Pathology of Endocrine system
Endocrine pathology is the subspecialty of diagnostic pathology which deals with the diagnosis and characterisation of neoplastic and non-neoplastic diseases of the endocrine system
When the pituitary Gland it' s function is increased whether the cause are?
Both anterior and Posterior gland secretions are increased the most causes are ADENOMAS
When the pituitary Gland it' s function is increased whether the cause are?
Both anterior and Posterior gland secretions are increased the most causes are ADENOMAS
this presentation was uploaded after my own need to find online presentation with the same content and had failed to find. My references were Robbins Pathology textbook, my lecturers notes and some chemistry pathology textbooks that i lack good memory of . I greatly apologize if the content appears copied or if its similar to another's. i also do apologize for improper grammar in some areas. If you find this set helpful please do tell me if you have time.
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
Explore our infographic on 'Essential Metrics for Palliative Care Management' which highlights key performance indicators crucial for enhancing the quality and efficiency of palliative care services.
This visual guide breaks down important metrics across four categories: Patient-Centered Metrics, Care Efficiency Metrics, Quality of Life Metrics, and Staff Metrics. Each section is designed to help healthcare professionals monitor and improve care delivery for patients facing serious illnesses. Understand how to implement these metrics in your palliative care practices for better outcomes and higher satisfaction levels.
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
India Clinical Trials Market: Industry Size and Growth Trends [2030] Analyzed...Kumar Satyam
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Growing Prevalence of Lifestyle Diseases
The rising incidence of lifestyle diseases such as diabetes, cardiovascular diseases, and cancer is a major trend driving the clinical trials market in India. These conditions necessitate the development and testing of new treatment methods, creating a robust demand for clinical trials. The increasing burden of these diseases highlights the need for innovative therapies and underscores the importance of India as a key player in global clinical research.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
The Importance of Community Nursing Care.pdfAD Healthcare
NDIS and Community 24/7 Nursing Care is a specific type of support that may be provided under the NDIS for individuals with complex medical needs who require ongoing nursing care in a community setting, such as their home or a supported accommodation facility.
2. The Endocrine system is divided into :
• Endocrine organs dedicated to production of
hormones e.g. pituitary,thyroid….etc
• Endocrine components in clusters in organs
having mixed functions e.g. pancreas, ovary,
testes…..
• Diffuse endocrine system comprising
scattered cells within organs acting locally
on adjacent cells without entry into blood
stream
3. Disease divided into :
1- Diseases of overproduction of secretion
( Hyperfunction )
2- Diseases of underproduction
( Hypofunction )
3- Mass effects ( Tumors )
N.B. Correlation of clinical picture , hormonal
assays , biochemical findings , together with
pathological picture are of extreme
importance in most conditions.
5. PITUITARY GLAND
• Pituitary in sella turcica,& weighs about 0.5gm.
• Connected to the HYPOTHALAMUS with stalk.
• Composed of :
A-ADENOHYPOPHYSIS- (80%)
– Blood supply is through portal venous plexus
– Hypothalamic-Hypophyseal feed back control
B- NEUROHYPOPHYSIS
– From floor of third ventricle
– Modified glial cells & axons hypothalamus.
– Has its own blood supply.
6. CELLS & SECRETIONS :
A- Anterior pituitary ( Adenohypophysis )
1-Somatotrophs from acidophilic cells → Growth H.
2- Lactotrophs from chromophobe cells → Prolactin
3- Corticotrophs from basophilic cells → ACTH,MSH .
4- Thyrotrophs from pale basophilic cells → TSH
5- Gonadotrophs from basophilic cells → FSH, LH
B- Posterior pituitary ( Neurohypophysis )
1- Oxytocin
2- ADH
7. HYPERPITUITARISM & PITUITARY ADENOMA
In most cases, excess is due to ADENOMA
arising in the anterior lobe.
Less common causes include :
* Hyperplasia
* Carcinoma
* Ectopic hormone production
* Some hypothalamic disorders
8. Pathogenesis of pituitary adenomas :
• Mutations in G-proteins ( α subunit) in the GNAS1
gene on chromosome 20q13 lead to activation
• 40% of GH secreting adenomas & less in ACTH
• G-proteins involved in signal transduction :
GDP GTP cAMP
• Mutations in α subunit interfere with GTPase function
• Mutations in RAS, overexpression in C- MYC & NM23
inactivation found in more aggressive tumor
• Other mutations : MEN-1 gene ( Menin)
G proteins
GTPase
9. Features common to all pituitary adenomas :
• 10% of all intracranial neoplasms & 25% incidental
3% occur with MEN syndrome
• 30-50 years of age
• Primary pituitary adenomas usually benign
• May or may not be functional
• If functional, the clinical effects are secondary to the
hormone produced.
• More than one hormone may be produced by same
cell
• Although most are localized, invasive adenomas
erode sella turcica & extend into cavernous &
sphenoid sinus
10. CLINICAL FEATURES of PITUITARY ADENOMA:
1- Symptoms of hormone produced
2- Local mass effects :
i- Radiological changes
ii-Visual field abnormalities
iii-Elevated intracranial pressure
3- Hypopituitarism
4- Pituitary apoplexy
11.
12.
13. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 4 December 2005 01:50 PM)
Mass effect of pituitary adenoma
14. Morphology of pituitary adenomas :
• Well circumscribed,invasive in up to 30%
• Size 1cm. or more, specially in nonfunctioning
tumor
• Hemorrhage & necrosis seen in large tumors
Microscopic picture :
• Uniform cells, one cell type (monomorphism)
• Absent reticulin network
• Rare or absent mitosis
16. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 4 December 2005 01:50 PM)
Uniform cells of pituitary adenoma
17. Types of Pituitary Adenomas
• Previously classified according to histological
picture e.g :
Acidophilic Adenoma
• Now according to immunohistochemical
findings & clinical picture ….. e.g.
Growth hormone secreting adenoma
19. 1- PROLACTINOMA :
• 30% of all adenomas, chromophobe or weakly
acidophilic
• Functional even if small, but related to size
• Other causes of prolactin include : estrogen
therapy, pregnancy, reserpine , hypothyroidism……
• Any mass in the suprasellar region may interfere
with normal prolactin inhibition Prolactin
( STALK EFFECT )
• Mild elevation of prolactin does NOT always indicate
prolactin secreting adenoma !
21. 2- Growth hormone secreting adenoma :
• 40% Associated with GNAS 1 gene mutation
• Persistent secretion of growth hormone leads
to secretion of Insulin – like GF → symptoms
• Composed of granular ACIDOPHILIC cells
• May be mixed with prolactin secretion.
• Symptoms delayed so adenomas are usually
large
• Produce GIGANTISM or ACROMEGALLY
• Other symptoms : diabetes, arthritis, large
jaw & hands, osteo porosis, BP, HF…..etc
22. 3- Corticotroph cell adenoma
• Usually microadenomas
• Higher chance of becoming malignant
• Chromophobe or basophilic cells
• Functionless or Cushing ‘s Disease ( ACTH )
• Bilateral adrenalectomy or destruction may
result in aggressive adenoma:
Nelson’s Syndrome
• Corticotroph microadenoma Macroadenoma
• ICP
23. 4- Non functioning adenoma 20%
silent or null cell ,nonfunctioning & produce mass
effect only
5- Gonadotroph producing LH &FSH- ( 10-15%)-
Function silent or is minimal , late presentation
mainly mass effect produced.
Produce gonadotrophin α subunit, β- FSH & β-LH
6- TSH producing ,(1%) rare cause of
hyperthyroidism
7- Pituitary carcinoma - Extremely rare, diagnosed
only by metastases.
24. HYPOPITUITARISM :
• Loss of 75% of ant. Pituitary Symptoms
• Congenital or acquired, intrinsic or extrinsic
• Symptoms include dwarfism, & effect of individual
hormone deficiencies. Loss of MSH → Decreased
pigmentation
• Acquired causes include :
1- Nonsecretory pituitary adenoma
2- Ischemic necrosis e.g.
SHEEHAN’S SYNDROME (post partum hmg.)
sickle cell anemia, DIC, Pituitary apoplexy…
3- Iatrogenic by radiation or surgery
4- Autoimmune ( lymphocytic) hypophysitis
5- Inflammatory e.g sarcoidosis or TB …..
25. 6- Empty Sella Syndrome : Radiological term
for enlarged sella tursica, with atrophied or
compressed pituitary.
May be primary due to downward bulge of
arachnoid into sella floor compressing
pituitary.
Secondary is usually surgical.
7- Infiltrating diseases in adjacent bone e.g.
Hand Schuller – Christian Disease
8- Craniopharyngioma
26. Craniopharyngioma :
* 1-5 % of intracranial neoplasms
* Derived from remnants of Rathke’s Pouch
* Suprasellar or intrasellar ,often cystic with
calcification
* Children or adolescents most affected
* Symptoms may be delayed ≥ 20yrs( 50%)
* Symptoms of hypofunction or hyperfunction
of pituitary and /or visual disturbances,
diabetes insipidus
* Benign & slow growing
27. POSTERIOR PITUITARY SYNDROMES:
1-A- ADH deficiency causes Diabetes Insipidus
Excessive urination,dilute urine , due to
inability to reabsorb water from the
collecting tubules. Causes include head
trauma, tumors & inflammations in pituitary
or hypothalamus…etc.
B- Syndrome of inappropriate ADH secretion
Causes excessive resorption of water
hyponatremia e.g Small Cell CA of Lung
28. 2-Abnormal oxytocin secretion :
Abnormalitis of synthesis & release have not
been associated with any significant
abnormality.
30. • Development from evagination of pharyngeal
tissue into neck
• Abnormal descent Lingual thyroid ,
subhyoid, substernal
• Weight 15-20gm. Responsive to stress
• Structure : varying sized follicles lined by
columnar epithelium , filled with colloid,
interfollicular C cells
• Secretion of T3 & T4 is controlled by trophic
factors from hypothalamus & ant.pituitary
31. THYROTOXICOSIS:
• Hypermetabolic state caused by T4, T3.
A- Associated with hyperthyroidism:
Primary : Graves Disease
Toxic multinodular goiter
Toxic adenoma
Secondary : TSH secreting pit. adenoma
B- Not associated with hyperthyroidism :
Thyroiditis
Struma ovarii
Exogenous thyroxine intake
35. Diagnosis of Hyperthyroidism :
• Measurement of serum TSH (↓ ) + free T4 is
the most useful screening test for
thyrotoxicosis
• TSH level is normal or in secondary
thyrotoxicosis
• In some patients , T3 but T4 normal or ↓
• Measurement of Radioactive Iodine uptake is
a direct indication of activity inside the gland
37. HYPOTHYROIDISM :
Primary :
1- Loss of thyroid tissue due to surgery or
radiation Rx.
2- Hashimoto’s thyroiditis
3- Iodine deficiency specially in endemic areas
4- Primary idiopathic hypothyroidism
5- Congenital enzyme deficiencies
6- Drugs e.g. iodides, lithium…..
7- Thyroid dysgenesis ( developmental )
Secondary :
Pituitary or hypothalamic failure
38. Hypothyroidism is commoner in endemic areas
of iodine deficiency
CRETINISM : hypothyroidism in infancy & is
related to the onset of deficiency .
If early in fetal life Mental retardation ,
short stature, hernia, skeletal abnormalities,
MYXEDEMA in adults Apathy, slow mental
processes, cold intolerence,accumulation of
mucopolysaccharides in subcutaneous tissue
Lab.tests : TSH in primary hypothyroidism,
unaffected in others T4 in both.
40. HASHIMOTO’s THYROIDITIS :
Chronic Lymphocytic Thyroiditis
• Autoimmune disease characterized by
progressive destruction of thyroid tissue
• Commonest type of thyroiditis
• Commonest cause of hypothyroidism in areas
of sufficient iodine levels
• F:M = 10-20 :1, 45-65 yrs.
• Can occur in children
41. Pathogenesis :
A - T cell sensitization to thyroid antigens
1- Sensitized CD4 T cells Cytokine mediated
( IFN- γ)cell death inflammation,macrophage
activation
2- CD8+ cytotoxic T cell mediated cell death:
Recognition of AG on cell killed
3- Presence of thyroid AB Antibody dependent
cell mediated cytotoxicity by NK cells
B- Genetic predisposition :
↑ in relatives of 1st.degree
Association with HLA – DR 3 & DR- 5
42. Morphology:
• Gland is a smooth pale goitre, minimally
nodular, well demarcated.
• Microscopically :
- Dense infiltration by lymphocytes &
plasma cells
- Formation of lymphoid follicles, with
germinal centers
- Presence of HURTHLE CELLS
- With or without fibrosis
43. • Clinically :
– Painless symmetrical diffuse goiter
– May show initial toxicosis ( Hashitoxicosis ).
– Later marked hypothyroidism.
– Patients have risk of B-Cell lymphoma
45. SUBACUTE GRANULOMATOUS
THYROIDITIS :
• Middle aged , more in females. Viral etiology ?
• Self-limited (6-8w)
• Acute onset of pain in the neck , fever,
ESR, WBC
• Transient thyrotoxicosis.
• Morphology :
– Firm gland.
– Destruction of acini leads to mixed inflammatory
infiltrate.
– Neutrophils , Macrophages & Giant cells &
formation of granulomas
46. SUBACUTE LYMPHOCYTIC THYROIDITIS :
(Silent)
• Middle aged females & post partum patients
• Probably autoimmune with circulating AB
• May recur in subsequent pregnancies
• May progress to hypothyroidism
• Histology similar to Hashimoto’s thyroiditis
without Hurthle cell metaplasia
• Reidel’s Thyroiditis –
Dense fibrosis without prominent inflammation
? Considered as fibromatosis rather than thyroiditis
47.
48. GRAVE’S DISEASE :
• Commonest cause of endogenous
hyperthyroidism
• Age 20- 40 yrs.,
• M: F ratio is 1: 7
• More common in western races
49. Main features of GRAVES DISEASE :
1 - Thyrotoxicosis with smooth symmetrical
enlargement of thyroid
2 - Infiltrative ophthalmopathy with
exophthalmus in 40%
3- Pretibial myxedema in a minority
• Lab findings : T4, T3 , TSH
• Radioactive study: Diffuse uptake of
radioactive I
50. Pathogenesis of GRAVE’S DISEASE :
• Genetic etiology + Autoimmune processes
• GENETIC EVIDENCE :
• May be familial
• 60% concordance in identical twins
• Susceptibility is associated with
HLA-B8 & - DR3
• May exist with other similar diseases e.g.
SLE, Pernicious anemia, Diabetes type I,
Addison’s dis.
51. IMMUNE MECHANISMS :
• Antibodies to thyroid peroxisomes & thyroglobulin
• Patients develop autoantibodies to TSH receptor
– Thyroid Stimulating Immunoglobulin ( TSI) binds
to TSH receptor → thyroxin ***
– Thyroid Growth Stimulating Immunoglobulin
(TGI) → proliferation of thyroid epithelium
– TSH binding inhibitor immunoglobulins (TBIIs)
prevent TSH from binding to receptor
• Both stimulation & inhibition may coexist
52. Morphology :
• Smooth enlargement of gland with diffuse
hyperplasia & hypertrophy
• Lining epithelium of acini :
Tall & hyperplastic ± papillae
• Colloid :
Minimal thin colloid with scalloped edge
54. Changes in Extrathyroid tissue :
• Generalized lymphoid hyperplasia
• Ophthalmopathy : Edematous orbital
muscles &infiltration by lymphocytes
followed by fibrosis
• Thickening of skin & subcutaneous tissue
• Accumulation of glycosaminoglycans which
are hydrophilic
55. • Result :
Displacement of eyeball & exophthalmus →
redness, dryness, ulceration, infection in
conjunctiva
• Cause :
Expression of aberrant TSH receptor
responding to circulating anti TSH receptor
AB → inflammatory lymphocytic reaction
57. DIFFUSE NONTOXIC & MULTINODULAR GOITRE
GOITER = Enlargement of thyroid
Most common cause is iodine deficiency
impaired hormone synthesis TSH
hypertrophy & hyperplasia of follicles Goiter
Endemic : 10% of population have goiter
Sporadic : 1- Physiological demand
2- Dietary intake of excessive
calcium & cabbages…etc
3- Hereditary enzyme defects
58. MORPHOLOGY :
• Initially diffuse → nodular with degenerative
changes: colloid cysts, hemorrhage, fibrosis,
calcification
• If large may extend retrosternally
• Pressure symptoms are a common complaint
• Picture is that of varying sized follicles,
hemorrhage , fibrosis , cysts, calcification
• Patient is often EUTHYROID. but may be
toxic or hypofunctioning.
64. NODULES in the thyroid :
• Nodules in thyroid may be multiple or solitary
• Any solitary nodule in the thyroid has to be
investigated as some are neoplastic.
Investigations include FNA , Radioactive image
technique, Ultrasound, & (T4,T3 & TSH ) levels
• HOT nodule takes up radioactive substance
( functional)
• COLD nodule does not it take up
( nonfunctional )
67. General rules of nodules in the thyroid :
1- Solitary nodule is MORE likely to be
NEOPLASTIC than multiple
2- Hot nodules are more likely to be BENIGN
3- Not every cold nodule is malignant .
Many are nonfuctioning adenomas, or colloid
cysts , nodules of nodular goitre….etc
Up to 10% of cold nodules prove to be
malignant.
68. 4- Nodules in younger patients are more likely
to be NEOPLASTIC
5- Nodules in males are more likely to be
NEOPLASTIC .
6- History of previous radiation to the neck is
associate with increased risk of malignancy
69. NEOPLASMS of the THYROID :
ADENOMAS:
• Usually single.
• Well defined capsule
• Commonest is follicular± Hurthle cell change
• May be toxic
• Size 1- 10cm. Variable colour
• Activating somatic mutation in TSH receptor is
identified leading to overproduction of cAMP
• 20% have point mutation in RAS oncogene
70. Microscopical Picture :
• 1- Uniform follicles , lined by cuboidal epithelial
cells.
• 2- Focal nuclear pleomorphism, nucleoli ….
( Endocrine atypia )
• 3- Presence of a capsule with tumor compressing
surrounding normal thyroid outside .
* Integrity of capsule is important in differentiating
adenoma from well differentiated follicular
carcinoma.
• Capsular and/ or vascular invasion →Carcinoma
74. CARCINOMAS of THYROID :
• Incidence about 1-2% of all malignancies.
• Wide age range ,depending on type.
• Generally commoner in females, but in
tumors occurring in children or elderly ,
equal incidence in both sexes.
• Most are derived from follicular cells
• Few are derived from ‘C’ cells
75. TYPES of THYROID CARCINOMA :
1- Papillary Carcinoma ( 75- 85% ),any age,but usual
type in children.
2- Follicular Carcinoma ( 10- 20% )More in middle age
3- Medullary Carcinoma ( 5% ) age 50-60 but younger
in familial cases with MEN syndrome
4- Anaplastic Carcinoma ( 5% ) , old age
Presenting symptom is usually a mass , maybe
incidental in a multinodular goitre specially papillary,
& follicular
76. Pathogenesis of Thyroid Cancer :
1- Genetic lesions :
Most tumors are sporadic
Familial is mostly Medullary CA , Papillary CA
• Papillary CA :
– Chromosomal rearrangement in tyrosin
kinase receptor gene (RET) on chr.10q11
ret/PTC tyrosine kinase activity
( 1/5 of cases specially in children)
– Point mutation in BRAF oncogene (1/3-1/2)
77. • Follicular Carcinoma :
– RAS mutation in ½ of cases OR
– PAX8- PPAR γ 1 fusion gene in 1/3 of
cases
• Medullary Carcinoma :
– RET mutation Receptor activation
• Anaplastic Carcinoma :
– Probably arising from dedifferentiation of
follicular or papillary CA inactivation of
P53
78. 2- Environmental Factors :
• Ionizing radiation specially in first two
decades
• Most common is Papillary CA. with RET
gene rearrangement
3- Preexisting thyroid disease :
• Incidence of thyroid CA is more in endemic
areas
• Long standing multinodular goiter →
Follicular CA
• Hashimotos thyroiditis → Papillary CA &
B cell lymphoma
82. Diagnosis based on NUCLEAR FEATURES
• Nuclei are clear (empty) ,with grooves &
inclusions ( Orphan Annie nuclei)
• Psammoma bodies
• Metastases mainly by L.N., sometimes from
occult tumor
• Hematogenous spread late & prognosis is
GOOD
86. FOLLICULAR CARCINOMA :
• Usually cold but rarely functional ( warm )
• Well circumscribed with thick capsule
(minimally invasive) or diffusely infiltrative
• Composed of follicles , sometimes of
Hurthle Cells
• Diagnosis is based on CAPSULAR &
VASCULAR invasion
87. • Metastasize usually by blood Lungs,
Bone, Liver ..etc.
• Treatment by surgery Radioactive Iodine
Thyroxin
• Prognosis is not as good as papillary except
in minimally invasive very well differentiated
forms
90. MEDULLARY CARCINOMA:
• Arise from C cells CALCITONIN, CEA,
serotonin, VIP
• 80% Sporadic , or familial MEN Syndrome
• Composed of polygonal or spindle cells ,
usually with demonstrable AMYLOID in the
stroma
• Calcitonin demonstrated in tumor cells
91. • Level of calcitonin in serum may be useful
for follow up
• Family members may show C cell
hyperplasia ,↑ Calcitonin, & RET mutation
( Marker for early diagnosis)
• Metastases by blood stream
• Prognosis intermediate , worse in MEN. 2B
94. ANAPLASTIC CARCINOMA :
• Elderly patients with multinodular goitre in
50%
• Foci of papillary or follicular CA may be
present in 20%- 30% , probable
dedifferentiation process
• Markedly infiltrative tumor , invading the
neck → pressure on vital structures
• Rapid progression, death within 1 year
95. • Morphology : Composed of pleomorphic
giant cells, spindle cells or small cell
anaplastic varients, which may be confused
with lymphoma
• Radiosensitive tumor , no surgery
• P53 mutation identified , consistent with
tumor progression
96. PARATHYROID GLAND
• Derived from the third and fourth pharyngeal pouches.
• 90% of people have four glands.
• Location: mostly close to the upper or lower poles of
the thyroid.
• Can be found anywhere along the line of descent of
the pharyngeal pouches.
• There are two types of cells with intervening fat :
- Chief & Oxyphil cells
• Secretion of PTH is controlled by level of free calcium
97. Hyperparathyroidism : Primary OR Secondary
Primary Hyperparathyroidism:
• Commonest cause of asymptomatic hypercalcemia
• Female:Male ratio = 2-3 : 1.
• Causes : Adenoma 75%-80%
Hyperplasia 10-15%
Carcinoma < 5%
• Majority of adenomas are sporadic
• 5% familial associated with MEN-1 or MEN-2A
98. Genetic abnormalities :
• PRAD 1 on chromosome 11 q cell cycle
control cyclin D1 overexpression(10%-20%)
• MEN 1 on 11q13 is a cancer suppressor gene
- Germ line mutation in MEN-1 syndrome
loss of function cell proliferation
- *20% - 30% of sporadic cases may also show
mutation of MEN1
*Either of above may cause tumor or hyperplasia
99. • Biochemical findings :
PTH , Ca , ↓ phosphate ,alkaline
phosphatase
• In other causes of hypercalcemia, PTH is ↓
100. Gland morphology in Hyperparathyroidism
• Adenomas :
• Usually single , rarely multiple
• Well circumscribed, encapsulated nodule
(0.5-5g.)
• The cells are polygonal, uniform chief cells,
few oxyphil cells. Adipose tissue is minimal in
the tumor
• Compressed surrounding parathyroid tissue in
periphery, other glands normal or atrophic .
101.
102. • Hyperplasia :
Enlargement of all 4 glands.
Microscopically chief cell hyperplasia, or clear
cell, usually, in a nodular or diffuse pattern.
Note : Diagnosis of adenoma versus hyperplasia
may depend on the size of the other glands
103. Parathyroid carcinoma :
• Larger than adenoma (5-10g)
• Very adherent to surrounding tissue.
• Pleomorphism & mitoses not reliable criteria
for malignancy
• Most reliable criteria for malignancy are :
* Invasion
**Metastases
104. Morphology in other organs:
• Skeletal system:
– Bone resorption by osteoclasts, with fibrosis, cysts
formation and hemorrhage Osteitis Fibrosa
Cystica
– Collections of osteoclasts form ‘ Brown Tumors”
– Chondrocalcinosis and pseudogout may occur.
• Renal system:
– Ca. Stones. & Nephrocalcinosis.
• Metastatic calcification in other organs:
Blood vessels & myocardium , Stomach, Lung …etc
105. Hyperparathyroidism, clinical picture
• 50% of patients are asymptomatic.
• Patients show Ca & PARATHORMONE levels in
serum
• Symptoms and signs of hypercalcemia:
Musculoskeletal, Gastrointestinal tract, Urinary
and CNS symptoms
• Commonest cause of silent hypercalcemia .
• In the majority of symptomatic hypercalcemia
commonest cause is wide spread metastases to bone
113. DIABETES :
• Chronic disorder in which there is abnormal
metabolism, of carbohydrate, fat & protein ,
characterized by either relative or absolute
insulin deficiency, resulting in hyperglycemia.
• Most important stimulus that triggers insulin
synthesis from β cells is GLUCOSE
• Other agents stimulate insulin release
• Level of insulin is assessed by the level of
C - peptide
114. • Diagnosis :
1- Random glucose ≥ 200g / dL + symptoms
2- Fasting glucose of ≥ 126 / dL on more
than one occasion
3- Abnormal OGTT when glucose level is
more than 200g / dL 2hrs. after standard
glucose load of 75 g.
115. Classification :
Causes could be Primary in the pancreas OR
secondary to other disease conditions
Primary diabetes is classified into :
A- Type 1
B- Type 2
C- Genetic & Miscellaneous causes
Whatever the type, complications are the same
116. Type 1 :-
• Absolute deficiency of insulin due to β cell
destruction ( 10%)
• 90% of cells lost before metabolic
changes appear
• Age ≤ 20 yrs but may be latent
• Normal or decreased weight
• Ketoacidosis is common
117. Type 2 :
• Due to a combination of peripheral
resistance to insulin action & inadequate
secretory response by the pancreatic β cells
• Commoner ( 80 - 90% )
• Insulin normal (relative insulin deficiency)
• Patient is overweight
• Rare ketoacidosis
118. Type 3 : Miscellaneous causes
• Genetic defects :
– β cell function
e.g. Maturity Onset Diabetes of the Young
( MODY)caused by a variety of mutations
– Genetic defects of insulin processing or
action
e.g. Insulin gene or Insulin receptor
mutations
119. Secondary Miscellaneous Causes :
• Diseases of exocrine pancreas e.g. chronic
pancreatitis
• Endocrinopathies e.g. Cushing’s Syndrome,
Acromegally
• Infections e.g. CMV
• Drugs e.g. glucocorticoids
• Gestational diabetes
• Other genetic syndromes associated with
diabetes
121. Pathogenesis of Type 1 Diabetes :
1- Genetic susceptibility
2- Autoimmunity
3- Environmental factors
It is a combination of autoimmunity &
environmental insult in a person with a
known genetic susceptibility leading to
destruction of β cells
122. 1- Genetic susceptibility
– Principal susceptibility genes located in
region of MHC class II on chromosome 6p21
– 90% Associated with HLA- DR3,or HLA-
DR4, or both
– Racial predisposition, (Caucasians) but
majority have no family history
– 6- 20% familial ,< 40% in identical twins
– Second susceptibility gene encodes a T cell
inhibitory receptor (CTLA-4) interfering with
normal T cell function
123. 2- Autoimmunity -
• Presence of CD 8+ & CD 4+ in islet cells
“ Insulinitis”
• Presence of islet cell antibodies ( insulin &
GAD) in 80% of patients & in relatives several
months or years before onset
• Antibodies are highly selective against β cells
• Relatives at risk have similar AB years before
onset
• 10% - 20% other autoimmune disease
124. 3- Environmental factors
An environmental insult may damage β cells
rendering them antigenic.
• Viruses : measles , coxsackie , rubella
• Chemicals
• Cow’s milk
125. Pathogenesis of Type 2 diabetes :
1- Genetic factors
2- Insulin resistance & obesity
3 - cell secretion dysfunction
126. 1- Genetic factors :
– Genetic factors are more important than in
type 1 diabetes, but this is multifactorial
– 50% - 90% in identical twins
– risk by 20%-40% in first degree relatives
– No association with HLA & no autoimmune
basis
– Point mutation in insulin receptor identified
affecting signaling pathway but rare ( 1-5%)
127. 2 – Insulin resistance :
• Decrease ability of peripheral tissue to
respond to insulin
Early : insulin resistance → insulin
secretion due to compensatory of cell
mass
Later : relative insulin & cell mass to
20-50%
MAIN FACTOR IN INSULIN RESISTANCE IS
OBESITY
128. Explanation :
• Adipocytokines :
– Resistin ↑ obesity → Insulin resistance
– Leptin & Adiponectin contribute to insulin
sensitivity but are ↓in obesity → resistance
– PPAR γ is a nuclear receptor that regulates
level of adipocytokines
– FFA in tissues (lipotoxic effect) →
insulin resistance
129. 3- cell Dysfunction :
• Defective glucose recognition due to ↑ intracellular
levels of a mitochondrial protein ( UCP2) in β cells
• Amylin :
A protein normally produced by cells secreted with
insulin in response to food ingestion
Amylin accumulates outside cells, forming amyloid
like deposits & may impair cell glucose sensing.
Seen in up to 90% of cases of Type II diabetes
130. Pathogenesis of complications :
1- Nonenzymatic glycosylation of proteins
Glucose + Free amino acids
Later → Irreversible combination
Advanced Glycosylation End products =AGES
Measured by level of glycosylated Hb
( HbA1c)
AGES inactivate proteins & cross link with
more proteins, deposited in vessels,
renal glomeruli, …..etc
131. Effects :
Induce cytokine production, GF :
• ↑ vascular permeability
• ↑ procoaggulant activity
• ↑ fibroblasts & SM in ECM
Complications in blood vessels, kidney,
nervous system ….etc
Complications are proportional to the degree
of hyperglycemia of whatever type
132. 2- The Polyol Pathway
Persistent hyperglycemia facilitates entry
of glucose & its accumulation into some
cells & metabolized into
SORBITOL (a polyol) &
FRUCTOSE
Creation of osmotic gradient Influx of
fluid + Toxic
lens, retina, peripheral nerves, kidney…etc
133. 3- Activation of Protein Kinase C :
• Activation of signal transduction
• Leads to production of pro-angiogenic
factors (VEGF)
Important in retinal neovascularization
• Production of pro-fibrogenic factors → ↑ECM
& BM thickening
135. Pathology in the Pancreas
i -Type I :
- Leukocytic infiltration of islets ( T cells)
‘Insulinitis’ with progressive depletion of
cells.
- Later small indistinct or absent islets.
ii - Type II :
- Ill defined reduction in islet cell mass
- Fibrous tissue accumulation in some islets
- Amyloid deposition in islets
• Newborn of diabetic mother : islet cell hyperplasia
146. • Clinical Features in Diabetes :
Type 1 :
• Age < 20 , but some are latent (LADA)
• May present with metabolic acidosis, weight
loss, dehydration,& electrolyte imbalance.
Polyuria , Polydipsia, Polyphagia ( 3P’s)
• Findings : - Hyperglycemia
- Glucosuria ± Ketonuria
- Electrolyte imbalance
147. Type 2 :
• Age > 40yrs., often present incidentally
• Patients may have the 3 P’s symptoms of
complications
• Hyperosmolar nonketotic coma caused by
dehydration due to uncompensated
hyperglycemic diuresis.
• No keto acidosis
• Increased susceptibility to infections
150. Islet Cell Tumors of Pancreas :
• Include insulinomas, gastrinomas,
glucagonomas….etc
• Less frequent than pancreatic CA
• Maybe functioning or nonfunctioning
• Tumors ≤ 2 cm. diameter likely to be benign
• Associated clinical syndromes :
1- Hyperinsulinism (Insulinomas)
2- Zollinger - Ellison Syndrome
( Gastrinomas)
3- Multiple endocrine neoplasia (MEN)
151. Insulinoma :
• Commonest type
• Hypoglycemia ≤ 50 mg./dl.
• Attack precipitated by fasting or exercise, relieved by
eating or glucose administration
• Lab. : serum glucose , serum insulin
• Most tumors in pancreas but can be ectopic
• Most tumors solitary ( < 2cm.), can be multiple
• Majority are benign, 10% can be malignant
• Histologically difficult to diagnose malignancy
152. Gastrinomas :
• More in middle aged females
• Located in pancreas , duodenum or peripancreatic
tissue
• Single or multiple, or associated with other tumors
• > 50% locally invasive or have metastasized at
diagnosis
• Present with Zollinger- Ellison Syndrome
153. Zollinger - Ellison Syndrome :
– Peptic ulcer disease
– Ulcer features :
Multiple ulcers
Unusual locations specially jejunum
Intractable
– Gastrin hypersecretion
– Diarrhea in > 50% & may be the presenting
symptom
156. ADRENAL GLAND
• Weight of normal gland is 4 gm.
Adrenal Cortex - Derived from mesoderm & composed
of
1- Zona glomerulosamineralocorticoids (aldosteron)
2- Zona fasciculata glucocorticoids ( cortisol )
3- Zona reticularis estrogens & androgens
• Diseases are those of hyperfunction & hypofunction
& tumors
157. Adrenal Medulla –
• Derived from neural crest & is part of sympathetic
system.
• Composed of Chromaffin cells secreting catecholamines
• Diseases are mainly tumors
158. Congenital Anomalies
• Incidental finding of adrenal tissue in the
inguinoscrotal path , mainly in males
• Fusion of adrenals
• Congenital adrenal hyperplasia
• Ectopic tissue in adrenal : liver, thyroid & ovarian
tissue
159. ADRENOCORTICAL HYPERFUNCTION :
• There are 3 syndromes associated with hyperfunction:
1- Cushing’s Syndrome & Cushing’s Disease
2- Conn’s Syndrome & Hyperaldosteronism
3- Adrenogenital Syndrome
160. CUSHING’Syndrome
• Elevation of cortisol level , which occurs in one of four
ways
A- Endogenous causes :
i- ACTH*secreting pituitary microadenoma, few
macroadenomas, OR hyperplasia
(CUSHING’s DISEASE)
ii-Adrenal tumor or hyperplasia
iii- Paraneoplastic syndrome
161. B- Exogenous cause :
Steroid Therapy
Tests used are :
Level cortisol in plasma,or excretion of 17hydroxy
steroids in urine, diurnal pattern , level of ACTH, &
Dexamethasone Suppression test.
162. Morphology of adrenals in Cushing’s Syndrome :
• This depends on the cause :
1- Exogenous increase glucocorticoids ACTH
Bilateral atrophy of adrenals
2 -Endogenous hypercorticolism:
a- Presence of adrenal adenoma or carcinoma,
with atrophy of adjacent & contralateral adrenal
b- Secondary to ACTH secreting adenoma
bilateral diffuse or nodular hyperplasia
c- Primary adrenal nodular hyperplasia
163.
164. The pituitary in all forms of Cushing’s syndrome shows
Alteration in ACTH producing cells :
• Granular basophilic cells show lighter homogenized
cytoplasm due to accumulation of intermediate keratin
filaments in cytoplasm , called :
• Crooke’s Hyaline Change
165. Clinical features of Cushing’s syndrome :
Main symptoms include :
Central obesity/ moon face
Hypertension
Hirsutism/ menstrual disturbances
Diabetes
Osteoporosis
Increased risk of infections
Pigmentation of skin
166.
167. HYPERALDOSTERONISM :
• Excess level of aldosterone cause sodium retension,
potassium excretion, resulting in hypertension &
hypokalemia.
• Type could be primary OR secondary
168. A- Primary : Conn Syndrome
• Caused by Adenoma (80%) F:M is 2:1
Single or multiple
• Or primary adrenal hyperplasia ( 15% ) ,
• Carcinoma is rare
• Adjacent adrenal cortex is NOT atrophic
• There is aldosteron Na retention & K excretion
BP , Hypokalemia , RENIN
Correctable cause of HYPERTENSION
169. B- Secondary :
Due to decreased renal perfusion,
activation of the renin - angiotensin system
aldosteron
• Differentiate from primary by RENIN
170. VIRILIZING Syndromes :
Could be caused by - primary gonadal disorders
- Adrenocortical Neoplasms
- Congenital adrenal hyperplasia
• Neoplasms can occur at any age, frequently malignant
• Congenital adrenal hyperplasia is caused by an enzyme
defect in cortisol synthesis (21 hydroxylase)
NO CORTISOLACTH androgenic steroids
• Virilization , precocious puberty, ambiguous genitalia
• Patients have risk for acute adrenocortical insufficiency
172. MORPHOLOGY in ALL ADRENAL TUMORS:
• Encapsulated , usually yellow
• Size variable 1-2 cm. ( 30gms.)Up to large tumors
• Most incidental nonfunctioning tumors, may be
functioning
• Malignant tumors with necrosis, hemorrhage (≥ 300gms)
• Usually larger , more aggressive in adults
• Both may show same appearance of uniform or slightly
pleomorphic cells ,may be eosinophilic or clear
• Local invasion ,& the presence of metastases
differentiate benign from malignant tumors
175. ADRENOCORTICAL INSUFFICIENCY :
• May be primary adrenal or secondary to destruction of
the pituitary as in SHEEHAN’s syndrome….etc
• Primary in adrenal may be :
A- Acute :
1- Massive adrenal hemorrhage as in anticoaggulant
therapy, DIC, sepsis by N.meningitidis,pseudomonas
( Waterhouse- Friderichsen syndrome)
2- Sudden withdrawal of steroid therapy
3- Stress in a pt.with underlying chronic insufficiency
178. Adrenal insufficiency (continued )
B- Chronic :( Addison’s disease )
Progressive destruction of the adrenal by :
1- Autoimmune Disorder: 75-90 % , may be sporadic
or familial, linked to HLA-B8 , DR3, HLA-DQ5
Often multisystem involvement
2- Infections e.g. Tuberculosis , fungii ( AIDS)
3- Metastatic tumors destroying adrenal e.g. lung,
breast , …others
179. Morphology & Clinical features in Chronic Adrenal
Insufficiency :
• Morphology depends on cause :
• Autoimmune :
Irregular small glands, cortex infiltrated by lymphocytes,
medulla normal.
• T.B. Caseating Granuloma
• Metastatic disease Type of primary tumor
• Secondary to pituitary cause : the adrenal is shrunken
180. • Clinical features :
Weight loss, hypotension, hypoglycemia, pigmentation….
There is Hyperkalemia & Hyponatremia due to
↓ mineralocorticoids
181. THE ADRENAL MEDULLA :
• Composed of CHROMAFFIN CELLS & nerve endings
• Secretetes cholamines in response to sympathetic
stimulation
• Also present in extra-adrenal sites
• Pathology includes tumors :
A- Pheochromocytoma
B- Neuroblastoma
182. PHEOCHROMOCYTOMA :
• Secretes catecholamines → VMA
• Sometimes described as The 10% Tumor because :
* 10% bilateral
* 10% extra adrenal ( Paraganglioma)
* 10% familial, maybe part of MEN syndrome
* 10% Malignant
• Usually well circumscribed,small to large in size,maybe
pleomorphic. Malignancy confirmed by METASTASES
• Clinically sustained or paroxysmal attacks of BP
• CORRECTABLE cause of HYPERTENSION
184. NEUROBLASTOMA :
• Commonest extracranial solid tumor of childhood
• Usually adrenal but maybe extra-adrenal
• Familial or sporadic
• Associated with deletion of short arm of chromosome 1
• 90% associated with catecholamine secretion
• VMA excreted in 24 hr. urine helpful in diagnosis.
• Morphologically it is composed of small round blue cells
which may differentiate to ganglion cells
• Spread to adjacent organs, lymph nodes, renal vein.
• Prognosis : STAGE , AGE , N myc amplification
186. POLYGLANDULAR SYNDROME :
• Autoimmune disease
• Familial or sporadic
– Isolated involvement of adrenals
– Multiorgan involvement
• Type I : autosomal recessive associated with mutation
on immune regulator gene on Chr. 21
• Type II : multifactorial, linked to
HLA-B8 , HLA-DR3 , HLA-DQ5
– Include Hashimoto’s thyroiditis,adrenalitis, diabetes type I,
pernicious anemia
187. MEN SYNDROME :
• Inherited syndrome with multiple endocrine tumors &
or hyperplasia of component cells
• Tumors occur at younger age
• Often preceded by asymptomatic OR symptomatic
hyperplasia in involved organ
• Tumors may be multifocal in the same organ
• Often more aggressive than the same tumor without
MEN syndrome
188. Types of MEN syndromes :
• Type MEN 1 : ( 3 Ps)
• Autosomal dominant
• Involves suppressor gene on 11q.13
– Parathyroid : multiglandular parathyroid
hyperplasia (95%]
– Pancreas: aggressive,multifocal functional
gastrinomas & insulinomas
– Pituitary: Prolactinoma ± GH
189. Type MEN 2 :
• Autosomal dominant Proto-oncogen mutation :
RET/10q 11
• MEN 2 A :
– Medullary carcinoma of thyroid + C cell hyperplasia
– Pheochromocytoma (50%)
– Parathyroid hyperplasia
• MEN 2 B :
– As above but no parathyroid hyperplasia
– Extra endocrine manifestations :
e.g. mucosal neurofibromas