Endocrine Diseases | Histopathology
Powerpoint + Slides + etc etc
Endocrine diseases are of three (3) types:
Overproduction of hormone
Underproduction of hormone
Mass occupying lesions (malignant or benign) (rare)
Pituitary gland
Has posterior lobe (80%) and anterior lobe (20%)
Composed of numerous cells secreting numerous trophic
hormones
Posterior lobe has direct connection with hypothalamus
Hypothalamus orchestrates the pituitary
Posterior pituitary gland hormones (2):
o Anti-diuretic hormone tries to maintain the body fluids
by fluid retention when blood pressure goes down
o Oxytocin assists and facilitates labor; dilates the cervix
and assists in contraction
Only ADH is related to disease; oxytocin does not have
any disease related to it
Hyperpituitarism
o Most commonly caused by adenomas
Benign lesions
Can be microadenomas or macroadenoma (by size)
Can be functional or non-functional
Can be hormone-negative (no secretion)
Can be a genetic mutation or sporatic (spontaneous)
o Pituitary adenoma
Pituitary is in the sella turcica under the brain; very
invasive procedure to operate on
Overgrowth of tumor can infringe surrounding blood
vessels & nerves:
Optic nerve Visual acuity
Blood vessels Deprivation of different parts of
the brain
Biopsy hallmark: Monomorphic cells look the same
as each other
Can increase the intracranial pressure
Can create visual field abnormalities
Can suddenly blead (apoplexy)
Can cause hypopituitarism
Prolactinoma
Most common dominant hormone secreted by
pituitary adenomas are prolactin
Important in lactation
Can develop in men; causes breast secretion
and loss of libido
Can develop in women; causes amenorrhea and
causes infertility
May be seen in pregnancy, drugs blocking
dopamine receptors
Treatment is laser-surgery because an open-
surgery is very invasive (stereotactic surgery)
Growth-hormone adenoma
Second most common type of pituitary adenoma
If adenoma develops before closure of long
bones causes gigantism
If adenoma develops after closure of long bones
causes acromegaly can cause dramatic
change in their face due to growth of face bones
o Can cause psychological effect
Diagnosis is through reconigition of increased
growth hormones which stimulates
somatomedin C induces increase in height
Corticotroph cell adenoma
Secretion of ACTHcortisol causing
hypercortisolism
Increase in body size concentrated creating
what is called a buffalo hump or truncal-
obesity
Others cause LH, FSH, TSH adenomas
Not as common
Pituitary carcinoma
Rare
Hypopituitarism
o Secondary to destruction of pituitary
o 75% of the parenchyma is lost; hypopituitarism is
already indicated
o May be secondary to trauma, brain surgery or pituitary
adenoma treated by laser surgery with over-removal of
pituitary gland
o Growth hormone deficiency
Dwarfism
o Gonadotropin deficiency
No LH & FSH
Lack of secondary sex characteristics
o TSH deficiency
Causes hypothyroidism
o Prolactin deficiency
More prominent in women
No release of breast milk even when pregnant
o MSH deficiency
Melanin
Causes pallor due to lack of pigment
ADH diseases
o Diabetes insipidus
Same manifestations as diabetes mellitus (polyuria,
polyphagia, polydipsia)
More extensive polyuria
Inability of the kidney to retain water from urine
May be caused by central (ADH problem) or
nephrogenic (unresponsive kidneys)
Loss of water causes high serum sodium
concentrations
o SIADH (Syndrome of inappropriate ADH secretion)
Causes dilution of sodium (hyponatremia)
Causes cerebral edema without peripheral edema
Thyroid gland
Composed of two (2) lobes found in the middle of the neck
During development, it is located at the back of the tongue
o Descend during development
Lingual thyroid
o Poor descent of the thyroid gland
o Behind the tongue
Ectopic thyroid
o Excessive descent of the thyroid gland
o At the level of the chest wall
Secretes T3 and T4 stimulated by TSH and acts in through
negative feedback inhibition
Increases basal metabolic rate
Important in brain development in developing children
o Reason why thyroid hormones are checked during
pregnancy
Goitrogens
o Food with not much nutrition (salads & leaves)
o Inhibit the function of thyroid glands
o Suppresses T3 and T4 synthesis
Causes overstimulation of TSH which causes
hyperplastic thyroid without hyperthyroidism
Iodine
o Helps in the synthesis of T3 and T4
Hyperthyroidism
o Most commonly caused by hyperplasia
o Type of thyrotoxicosis in which there is a
hypermetabolic state (Increased T3 and T4)
o Primary hyperthyroidism
Most common cause is hyperplasia
Problem coming from the thyroid
o Secondary hyperthyroidism
Problem coming from other organs affecting the
thyroid gland
o Over-activity of the sympathetic system
Sweating profusely
Tachycardia
Anxious & panicking
Irregular menstrual periods
o Presence of exophthalmos protrusion of the eye
Common sign of hyperthyroidism
o Diagnosis is by a depressed TSH or increased T3 and
T4 (usually T3 and T4 both elevated)
 o Graves disease
Triad of:
Myxedema (in the leg)
Hyperthyroidism
Exophthalmos
Autoimmune disease
Antibodies directed against TSH receptors (may
also be for the T3 and T4 hormones & thyroglobulin)
Stimulates hyperplasia of the gland
Biopsy hallmark: Overcrowded cells & scalloped
colloid
Hypothyroidism (Cretinism)
o Has primary & secondary hypothyroidism
o Congenital hypothyroidism
Part of newborn-screening
Must be found early to prevent mental retardation
o Myxedema (Gull disease)
Hypothyroidism in adults
Mental sluggishness & obesity
Poor retention (poor in class)
Some form of edema because of accumulation of
glycosaminoglycan & hyaluronic acid in
subcutaneous area
Increased TSH and decreased T3 and T4 (T3 may be
decreased at times but T4 is always decreased after
treatment)
Treatment is to supply thyroid hormones
o Hashimoto thyroiditis
Iodine is very important in hormone synthesis
Autoimmune disease
Breakdown of self-tolerance to thyroid antigens
Antibodies directed against thyroid tissue itself
Infiltrates of lymphocytes replace thyroid tissue
Biopsy hallmark: Lymphoid follicles with prominent
germinal centers
Usually found in lymphoid organs (tonsils, spleen,
Peyers patches in ileum)
Lymphoma can grow in places wherein lymphocytes
should not be normally seen
Prone to development of lymphoma in thyroid
Malignant lymphocytes
Prone to develop Hodgkins lymphoma and
susceptibility to other autoimmune disease
o Main risk factor of Hashimoto thyroiditis
Predominantly a hypothyroidism state
Stages of high-levels of thyroid hormones may
occur called hashotoxicosis but this subsides
and reverts to hypothyroidism state
o De Quervain thyroiditis
Development of viral infection causing inflammation
of thyroid afterwards
Stimulated by virus-induced host tissue damage
which stimulates T-lymphocytes causing damage to
the thyroid gland
Usually painful but heals in 6 8 weeks
Subacute lymphocytic thyroiditis
o Mild hyperthyroidism
Riedels thyroiditis
o Hardened and fixed that stimulates a carcinoma
o Benign
Goiter
o Enlarged thyroid gland
o Doesnt indicate malignant or benign conditions
o Maybe proportional to thyroid hormone deficiency
Paired synthesis of hormone caused by iodine
deficiency
TSH tries to stimulate synthesis of T3 and T4
lack of iodine causes failure of synthesis
euthyroid goiter
o Simple goiter
Simple nodule
May be endemic due to the lack of iodine in the
community (mountainous regions)
o Sporadic simple goiter
May happen following a diet that is rich in goitrogens
(has excessive calcium & acts against thyroid
hormones)
o Multinodular goiter
Continuous involution (small big) which creates
nodulation
Causes scarring & calcification producing nodules
Can infringe on the neck causing difficulty in
breathing, swallowing, talking and blood vessels
causing ischemia
Can cause compression of the lungs
Long-standing multinodular goiter gives rise to risk
of malignancy
Malignancy is diagnosed by radionuclide scanning
Hot nodule (functioning) usually benign
Cold nodule (non-functioning) usually
malignant; but can be benign upon biopsy
o If biopsy and radionuclide scanning oppose
each other, follow the biopsy results
o May probably be a benign tumor that
produces a cold nodule effect on the scan
Thyroid adenoma
o Benign as with all adenomas
o Unilateral painless mass
o Perceived as cold nodule; capsule that encloses the
tumor must be evaluated for differentiation from
malignancy
Thyroid carcinoma
o Mostly developing in adults
o Major causing factor is ionizing radiation particularly in
the first two (2) decades of life
o May also be due to long-standing multinodular goiter or
Hashimoto thyroiditis developing into lymphomas
o Papillary carcinoma (85%+)
Most common thyroid carcinoma
Papillary because arrangement of malignant cells
is leaf-life or papillae
Orphan-Anne eye (right)
Characterized by a blank-staring eye ~(O_O~)
Presence of Psammona bodies (left)
Common but not characteristic finding
May start as a asymptomatic simple nodule
Perceived as a cold nodule
Most common & indolent carcinoma
Painless and slow-growing
Chance-to-live more than 10 years is 95% if no
complications
Recurrence or relapse reduces 10-year survival rate
to 5 20%
Distant metastasis reduces 10-year survival rate to
10 15%
Prognosis depends on the age, extension, stage
o Follicular carcinoma (5 15%)
Common in areas with iodine deficiency
Spreads faster in the blood vessels than in the
lymphatics (unlike most carcinomas which spread
through the blood vessels)
 o Medullary carcimoma (5%)
Neuroendocrine tumors derived from C-cells
Secrete calcitonin
Which is measured for its diagnosis
Typical description: Grow in nests & trabeculae;
amyloid-deposits in the stroma (characteristic)
No hypocalcemia even if calcitonin levels are high
o Anaplastic carcinoma (<5%)
100% mortality in less than a year of diagnosis
Can spread to the lungs and the brain
Fast-spreading cancer and very fatal
Parathyroid gland
Located at the back of the thyroid
Four (4) in total; two (2) superior, two (2) inferior
Controlled by the level of calcium in the body
Decreased levels of calcium cause the increase of
secretion of PTH regulate calcium homeostasis
Hyperparathyroidism
o Excessive secretion of PTH
o Primary hyperparathyroidism:
Most commonly caused by an adenoma
MEN (multiple endocrine neoplastic syndrome)
Carcinoma of multiple endocrine organs such as
parathyroid, thyroid, pituitary etc
Manifestations in patients are skeletal and renal
changes because of calcium
If caused adenoma; it can be removed surgically
If hyperplasia; it can be treated medically
Carcinoma is quite rare
Overproduction of PTH
Biopsy hallmark: Monomorphic cells look alike
Can be asymptomatic or symptomatic
Can cause osteoporosis
Can caused development of stones (renal & gall)
Can cause neurological disturbances due to
problems with calcium
o Secondary & tertiary parathyroidism
Commonly due to renal failure
Mechanism is not quite clear
Joined with chronic end-stage renal disease
Due to loss of renal substance
Decrease in intestinal absorption of calcium
Treatment is parathyroidectomy
Hypoparathyroidism
o Commonly caused by surgery
Usually happens when there is surgical removal of
thyroid glands and parathyroid is accidentally
removed along with it (complication)
o May cause tetany (unwanted muscular movements),
depression, emotional disturbance, ocular
manifestations, dental abnormalities
o Can be treated with supplements
Pseudo-hypoparathyroidism
o Resistance to the action of PTH
o Organ is non-reactive to parathyroid hormone
Pancreas
Contains one-million (1,000,000) islets of Langerhans
Four major cell types:
o Beta cells (68%) insulin hypoglycemia
o Alpha cells (20%) glucagon hyperglycemia
o Delta cells (10%) somatostatin suppresses both
insulin & glucagon
o PP cells (2%) pancreatic polypeptide stimulation of
gastric & intestinal enzymes
Two minor cell types:
o DI cells
o Enterochromaffin cells
Diabetes Mellitus
o Group of metabolic disorders
o May be due to defective insulin section, action or both
o Diagnosis (3):
FBS 126+ mg/dL on more than one occassion
RBS 200+ mg/dL (with classical symptoms)
Abnormal OGTT wherein glucose is 200+ mg/dL two
(2) hours after a standard carbohydrate load
o Impaired glucose tolerance (IGT) FBS in 100 125
mg/dL range or OGTT values of 140 200 mg/dL
Considered as pre-diabetics
o Delay in development can be modulated by strict diet,
lifestyle change, etc.
o Glucose homeostasis is normally maintained by:
Glucose production in the liver
Uptake & utilization
Insulin & other regulating hormones
o Insulin
Increases rate of glucose transfer into the muscle
(skeletal muscle: major insulin-responsive site)
reason for intramuscular nature of injection
o Type I - diabetes mellitus (usually in children)
Lacks insulin production due to an autoimmune
disorder against the beta-cells of the pancreas
Insulitis autoantibodies against pancreatic cells
Hyperglycemia due to lack of insulin
Inheritances of class-II-MHC, HLA-B, R3, ER4
90 95% will develop diabetes
Risk factors include previous infections
coxsackievirus, mumps virus etc.
Requires islet-cell transplantation
Biopsy hallmarks: Reduced number & size of islets,
insulitis, beta-cell degranulation
o Type II diabetes mellitus (usually in adults)
Insulin-resistance on glucose uptake
More dependent on genetic factors than type I
Qualitative & quantitative defects
Hallmark: Amyloid-deposits (like medullary
carcinoma)
Fat content is inversely proportional to insulin
sensitivity
Antihyperglycemics (adipokines) improve insulin
sensitivity; reduce obesity
Inflammation can induce cytokines to promote
insulin resistance
Complications can be:
Macrovascular aorta
Microvascular kidney, eye vessels
Can cause formation of AGEs which cause free-
radical formation
Can cause neovascularization in the blood vessels
which increases vascular premability
Vasoconstriction
Biopsy hallmark: Subtle reduction of islet cell mass;
amyloid replacement
Atheroma can cause thrombosis embolus
may cause gangrene in foot infection
Poor wound-healing & resistance to infection
Life-style alteration & glycemic control
Insulinoma
o Secretes insulin constant hypoglycemia
Gastrinoma
o Secretes gastrin frequent peptic ulcer
Adrenal glands (suprarenal glands)
Three (3) zones of cortex:
o Glomerulosa mineralocorticoid, aldosterone
o Fasciculata glucocorticoids; cortisol
o Reticularis androgen & estrogen (sex hormones)
Medulla
o Cathecolamines epinephrine
Cushing syndrome
o Increased cortisol
o Central obesity; buffalo hump
o Diagnosis is by finding increased levels of cortisol
Hyperaldosteronism
o Primary hyperaldosteronism
Most common cause is an adenoma (Conn
syndrome)
Sodium retention & potassium excretion
Normally-used to maintain blood pressure
Hypernatremia and hypokalemia
Suppresses the RAAS system (negative feedback)
Need potassium (give banana lolwtf)
Secondary to adenoma; surgical removal
 Secondary to hyperplasia; treat medically
o Secondary hyperaldosteronism
Response to activation of RAAS
Adrenal insufficiency
o Primary hypoadrenalism
Due to primary adrenal disease which can be acute
or chronic
o Secondary hypoadrenalism
Decreased stimulation of adrenals due to deficiency
of ACTH
o Waterhouse-Friderichsen syndrome
Overwhelming bacterial (N. meningitidis) infection
Develops adrenocortical insufficiency associated
with massive bilateral adrenal hemorrhage due to
bacterial seeding of the small blood-vessels (DIC)
o Primary chronic adrenocortical insufficiency (Addison
disease)
Uncommon disorder (commonly caused by TB)
Due to progressive destruction of 90% of the
adrenal cortex
Adrenocortical neoplasm
o May be functional or nonfunctional
Pheochromocytoma
o Composed to chromaffin cells which synthesize
catecholamines
o Rule of 10
10% associated with familial syndromes
10% extra adrenal
10% bilateral
10% malignant
10% arise in childhood
o Hypertension
o Tachycardia, palpitations secondary to sympathetic
stimulation
o Congestive heart failure & ventricular fibrillation
o Diagnosis: Urinary excretion of catecholamines &
metabolites;
o Tests VMA & metanephrines pheochromocytoma
Multiple Endocrine Tumor
MEN, type 1
o Wermer syndrome
o 3 Ps
Pituitary glands
Parathyroid
Pancreas
MEN, type 2A
o Sipple syndrome
o Pheochromocytoma
o Medullary carcinoma
o Parathyroid hyperplasia
MEN, type 2B
o All of MEN-2A plus:
Neuromas
Ganglioneuromas
Marfanoid habitus
o 2B is 2A with added brain involvement
Familial medullary thyroid cancer
o Variant of MEN-2A
o Same clinical manifestations
o Genetic testing must be done to screen for mutation &
possible treatment prophylactic thyroidectomy
Pineal gland
Composed of loose, neuroglial stroma enclosing nests of
pineocytes (cells with photosensory & neuroendocrine
function)
3rd eye
Lesion in pineocytoma can cause sightings
AngeloBautista