PATHOLOGY OF THE ENDOCRINE
SYSTEM 2
DR IZEIN NARUGAYAM CLAUDIUS
DEPT OF ANATOMICAL PATHOLOGY
NDU
OUTLINES
Ò DXS OF THE ENDOCRINE PANCREAS
Ò DXS OF THE ADRENAL GLAND
Ò DXS OF THE PINEAL GLAND
ENDOCRINE PANCREAS
Composed of clusters of cells termed islets of
Langerhans.
A single islet consists of multiple cell types, each
producing one type of hormone.
Insulin is secreted by beta cells, which lie in the center
of the islets.
1. Major anabolic hormone; upregulates insulin-
dependent glucose transporter protein (G1.UT4) on
skeletal muscle and adipose tissue (glucose uptake
by GLUT4 decreases serum glucose)
2. Increased glucose uptake by tissues leads to
increased glycogen synthesis, protein synthesis, and
lipogenesis,
Glucagon is secreted by alpha cells; it opposes insulin
in order to increase blood glucose levels (e.g., in
states of fasting) via glycogenolysis and lipolysis.
DIABETES MELLITUS
Definition:
Ò DM is a group of metabolic disorders sharing
the common underlying feature of
hyperglycaemia.
Ò Hyperglycaemia in DM results from defects
in insulin secretion, insulin action or most
commonly both.
Ò The chronic hyperglycaemia and attendence
metabolic dysregulation may be associated
with secondary damage in multiple organ
system especially the kidneys, eyes, nerves
and blood vessels.
DIABETES MELLITUS
EPIDEMIOLOGY:
Ò DM is a leading cause of endstage renal
disease, adult onset blindness and non
traumatic lower extremity amputation in US.
Ò Worldwide, more than 140 million people
suffer from DM, making it one of the most
common non-communicable diseases.
Diagnosis
Ò Normal blood glucose 70-120 mg/dL
Ò DM is diagnosed when there is
Ò A random glucose level of > 200mg/dl or 11
mmol/l, with classical signs and symptoms.
Ò A fasting glucose of >126 mg/dl(7mmol/l) in
more than one occasion.
Ò An abnormal OGTT in which glucose is
200mg/dl 2hrs after a standard
Carbohydrate load.
Note that
Ò Fasting blood glucose >120mg/dL but
<126mg/dl is impaired glucose tolerance
(IGT).
Ò Also OGTT level greater than 140mg/dl but
less 200mg/dl is IGT.
Ò IGT people have a significant risk of
progressing to overt DM overtime.
Ò Also those with IGT are at risk for
cardiovascular disease due to abnormal CHO
metabolism as well as the co-existence of
other risk factors such as LDL,
Hypertriglyceloraemia and increase
CLASSIFICATION OF DM
The vast majority of cases of DM fall into
1. Type I diabetes (10% of all cases: an absolute
deficiency of insulin caused by B-cell destruction,
which can be
-- immune mediated.
-- Idiopathic
2. Type 2 diabetes (about 80-90% of all cases): relative
insulin deficiency caused by a combination of
peripheral resistance to insulin action and or
inadequate secretory response by pancreatic B cells.
3. Genetic defects of B- cell function.
A. Maturity-onset diabetes of the young (MODY)
caused by mutation in different factors involved in
metabolism of insulin (MODY 1-6).
B. Mitochondrial DNA mutations.
4. Genetic defects in insulin processing or
insulin action.
Ò Defects in pro insulin conversion.
Ò Insulin gene mutations.
Ò Insulin receptor mutations.
5. Exocrine pancreatic defects
Ò Chronic pancreatitis.
Ò Pancreatectomy.
Ò Neoplasm.
Ò Cystic fibrosis.
Ò Haemachromatosis.
Ò Fibrocalculus pancreatopathy
6. Endocrinopathies
Ò Acromegaly.
Ò Cushing syndrome.
Ò Hyperthyroidism.
Ò Pheochromocytoma.
Ò Glucagonoma.
7. Infections
Ò Cytomegalovirus.
Ò Coxsackie virus B
8. Drugs
Ò Glucorticoids.
Ò Thyroid hormones.
Ò Alpha interferon.
Ò Protease inhibitors.
Ò B-adrenegic agonists.
Ò Thiazides.
Ò Niconitic acid
Ò Phenytoin.
9. Genetic syndromes associated
with Diabetes.
Ò Down syndrome.
Ò Kleinfelter syndrome.
Ò Turner syndrome.
10. Gestational diabetes mellitus.
TYPE 1 DIABETES MELLITUS
Insulin deficiency leading to a metabolic
disorder characterized by hyperglycemia
Due to autoimmune destruction of beta cells by
T lymphocytes
Ò 1. Characterized by inflammation of islets
Ò 2. Associated with HLA-DR3 and HLA-DR4
Ò 3. Autoantibodies against insulin are often
present (sign of damage) and may be seen
years before clinical disease develops.
Pathogenesis of Type 1 DM
Ò This results from severe lack of insulin caused by
immunologically mediated destruction of B-cells.
Ò Type 1 DM most commonly develops in childhood,
becomes manifest at puberty and progresses with
age.
Ò Since it can develop at any age including late
adulthood, the term “juvenile diabetes”is now
considered obsolate.
Ò Type 1 diabetes is an autoimmune disease in
which islet destruction is caused primarily by T
lymphocytes reacting against as yet poorly defined
B-cell antigens.
Ò As in all autoimmune diseases, genetic
susceptibility and environmental factors play
important roles in the pathogenesis
Genetic susceptibility
Ò The most important of the multiple loci
associated with type I DM is Class II MHC
(HLA) locus which contributes more than half
of the genetic susceptibility. All others make
up the other half.
Ò Thus, DQBI 0302 allele is considered the
primary determinant for susceptibility for the
HLA-DR4 haplotype; in contrast, the HLA-
DQBI 0602 allele is considered protective
against diabetes.
Non-MHC genes
Ò Increased susceptibility to disease is
associated with polymorphisms in the
promoter region of the insulin gene.
Ò Pts with type 1 DM show increased
frequency of a splice variant of the gene
encoding the T-cell inhibitory receptor
CTLA-4. This variant alternates with the
normal ability of this receptor to keep self-
reactive T lymphocyte under control.
Environmental factors
Infections
Ò Viruses e.g Coxsackie viruses group B is
associated with pancreatic diseases
including diabetes.
Ò Mumps, measles, CMV, rubella and
infectious mononucleosis are other
implicated viruses.
Ò These viruses do not cause diabetes by
directly damaging B-cells.
Two mechanism which are not mutually
exclusive have been proposed
Ò The infections induce tissue damage and
inflammation, leading to the release of B-cell
antigens and the recruitment and activation of
lymphocytes and other inflammatory
leukocytes in the tissue.
Ò Other possibility is that the viruses produce
proteins that mimic self-antigens and the
immune response to the viral protein cross-
reacts with the self-tissue. Neither is
established.
Manifests in childhood with clinical features of
insulin deficiency
I. High serum glucose—Lack of insulin leads to
decreased glucose uptake by fat and skeletal
muscle
2. Weight loss, low muscle mass, and
polyphagia—Unopposed glucagon leads to
gluconeogenesis, glycogenosis and lipolysis,
which further exacerbates hyperglycemia.
3. Polyuria, polydipsia, and
glycosuria—Hyperglycemia exceeds renal ability
to resorb glucose; excess filtered glucose leads
to osmotic diuresis.
Treatment involves lifelong insulin
Risk for diabetic ketoacidosis
Characterized by excessive serum ketones
Often arises with stress (e.g., infection);
epinephrine stimulates glucagon secretion
increasing lipolysis {along with
gluconeogenesis and glycogenolysis),
I. increased lipolysis leads to increased free
fatty acids (FFAs).
ii. Liver converts FFAs to ketone bodies (|3-
hydroxybutyric acid and acetoacetic acid).
Results in hyperglycemia (> 300 mg/dl.), anion
gap metabolic acidosis, and hvperkalemia.
Presents with Kussmaul respirations,
dehydration, nausea, vomiting, mental
status changes, and fruity smelling
breath (due to acetone)
Treatment is fluids (corrects dehydration from
polyuria), insulin, and replacement of
electrolytes (e.g., potassium).
TYPE 2 DIABETES MELLITUS
End-organ insulin resistance leading to a
metabolic disorder characterized by
hyperglycemia
Most common type of diabetes (90% of
cases}; affects 5-10% of the US population.
Incidence is rising.
Arises in middle-aged, obese adults
1. Obesity leads to decreased numbers of
insulin receptors.
2. Strong genetic predisposition exists.
PATHOGENESIS OF TYPE 2 DM
Ò Its pathogenesis has remained enigmatic.
Ò Environmental factors such as sedentary
life styles and dietary habits both of which
are linked by obesity clearly play a role.
Ò Genetic factors are even more important
than in type 1 diabetes. Among identical
twins, the concordance rate is 50% to 90%,
while among 1st degree relatives with the
type 2 diabetes (and in fraternal twins) the
risk of developing the disease is 20% to 40%,
compared to 5% to 7% in the general
population.
But unlike type 1 DM, type 2 DM is not linked
to genes involved in immune tolerance and
regulation, and there is no evidence to
suggest an autoimmune basis for type 2 DM
Two metabolic defects characterize type 2
DM
Ò A decreased ability of peripheral tissues to
respond to insulin (insulin resistance).
Ò B – cell dysfunction that is manifested as
inadequate insulin secretion in the face of
insulin resistance and hyperglycaemia.
In most cases, insulin resistance is the
primary event and is followed by increasing
degrees of B-cell dysfunction.
B-cell dysfunction
Ò In the type 2 DM, this connotes the inability
of these cells to adapt themselves to the
long-term demands of peripheral insulin
resistant and increased insulin secretion..
TYPE 2 DIABETES MELLITUS
Insulin levels are increased early in disease, but
later, insulin deficiency develops due
to beta cell exhaustion; histology reveals amyloid
deposition in the islets (Fig. 15.12).
Clinical features include polyuria, polydipsia,
and hyperglycemia, but disease is often
clinically silent.
Diagnosis is made by measuring glucose levels
(normal is 70-120 mg/dL).
1. Random glucose > 200 mg/dL
2. Fasting glucose > 126 mg/dL
3. Glucose tolerance test with a serum glucose
level > 200 mg/dL two hours after glucose
loading.
TYPE 2 DIABETES MELLITUS
Treatment involves weight loss (diet and
exercise) initially; may require drug therapy
to counter insulin resistance (e.g.,
sulfonylureas or metformin) or exogenous
insulin after exhaustion of beta cells.
Risk for hyperosmolar non ketotic coma
1. High glucose (> 500 mg/dL) leads to life-
threatening diuresiswith hypotension and
coma.
2. Ketones are absent due to small amounts of
circulating insulin.
MONOGENIC FORMS OF
DM
Ò Monogenic causes of diabetes result from
either a primary defect in B-cell function or a
defect in insulin/insulin receptor signaling.
1. Maturity-onset Diabetes of the young
(MODY): This represents 2-5% of diabetic
patients who do not fall clearly into either
type 1 or type 2 diabetes phenotype.
MONOGENIC FORMS OF DM
2. Mitochondrial diabetes: Mitochondrial
DNA is inherited maternally and encodes
several genes in the oxidative
phosphorylation pathway, ribosomal RNAs
and 22 transfer RNAs (tRNAs). Less than
1% of diabetes is associated with point
mutations in the mitochondrial tRNA gene,
tRNA. Leu (UUR) 91.
Mitochondial DM is caused by a primary
defect in B-cell functions.
MONOGENIC FORMS OF DM
3. Diabetes associated with insulin gene or
insulin receptor mutations.
These are mutations that affect insulin
processing from it’s precursor (pro-insulin) .
Or those that affect insulin structure and
binding to its receptor.
They are rare causes of diabetes
LONG-TERM CONSEQUENCES OFF
DIABETES
Nonenzymatic glycosylat ion (NEG) o f the
vascular baseme nt membrane
NEG of large- and medium-sized vessels
leads to atherosclerosis and its resultant
complications,
i. Cardiovascular disease is the leading cause
of death among diabetics.
ii. Peripheral vascular disease in diabetics is
the leading cause of non-traumatic
amputations.
NEG of small vessels (arterioles) leads to
hyaline arteriolosclerosis.
i. Involvement of renal arterioles leads to
glomerulosclerosis, resulting in small, scarred
kidneys with agranular surface.
ii. Preferential involvement of efferent arterioles
leads to glomerular hyper hit ration injury with
microalbuminuria that eventually progresses to
nephrotic syndrome; characterized by
Kimmelstiel-Wilson nodules in glomeruli
NEG of hemoglobin produces glycated
hemoglobin (HbA!C), a marker of glycemic
GLOMERULOSCLEROSIS.
HYALINE ARTERIOLOSCLEROSIS.
Osmotic damage
1. Glucose freely enters into Schwann cells
(which myelinate peripheral nerves),
pericytes of retinal blood vessels, and the
lens.
2. Aldose reductase converts glucose to
sorbitol, resulting in osmotic damage.
3. Leads to peripheral neuropathy, impotence,
blindness, and cataracts; diabetes is the
leading cause of blindness in the developed
world.
PATHOGENESIS OF THE
COMPLICATIONS OF DIABETES
Ò Macrovascular diseases – involving large and
medium sized muscular arteries.
Ò Microvascular diseases – Capillary dysfunction
in target organs.
Macrovascular disease causes:
Ò Accelerated atherosclerosis among diabetes.
Resulting in increased risk of MI, stroke and lower
extremity gangrene.
Effects of microvascular disease are most profound
in the retina, kidneys and peripheral nerves
resulting in diabetic retinopathy, nephropathy
and neuropathy respectively
.
Ò Most of the available experimental and
clinical evidence suggests that the
complications of diabetes are a
consequence of the metabolic
derangements, mainly hyperglycaemia
Ò At least three distinct metabolic pathways
appear to be involved in the pathogenesis
of long-term diabetic complications.
1. Formation of advanced glycation end
products. AGEs are formed as a result
of nonenymatic reactions between
intracellular glucose-derived dicarbonyl
precursors (glyoxal, methyglyoxal and 3-
deoxyglucosone) with the amino group of
both intracellular and extracellular
proteins.
AGEs have a number of chemical and
biologic properties that are detrimental to
ECM components and the target cell of
diabetic complications (endothelial cells).
MORPHOLOGY OF DIABETES AND
IT’S LATE COMPLICATIONS
Ò The morphologic changes are related to
the many late systemic complication of
diabetes.
Ò There is extreme, variability among
patients in the time of onset, severity
and the organ(s) affected for this
complications.
Those with tight control of diabetes, onset
may be delayed,.
However, in most diabetics, morphologic
changes are likely to be found in
Ò Arteries (macrovascular disease),
Ò Basement membrane of small vessels
(microangiopathy),
Ò Kidneys (diabetic nephropathy),
Ò Retina (retinopathy)
Ò Nerves (neuropathy) and
Ò Other tissues, for both type I and 2
diabetes.
MORPHOLOGY (PANCREAS)
Lesions are inconstant and rarely of diagnostic
value:
1. Reduction in the size and number of islets.
2. Leucocytic infiltration of the islets (insulitis) –
type 1.
- Mainly of T lymphocytes.
- Eosinopholic infiltrates may also be found
particularly in diabetic infants.
3. Amyloidosis of pancreatic islets – Type 2
diabetes.
Ò Increase in the number and size of islets
especially characteristic of nondiabetic
newborns of diabetic mothers.
Ò Diabetic macrovascular disease
(DMD)
Ò Hallmark of DMD is accelerated
atherosclerosis involving the aorta, large and
medium sized arteries. Compared to non-
diabetes, the atherosclerosis is earlier in onset
and is more severe.
Ò Myocardial Infarction caused by
atherosclerosis is the most common cause of
death in diabetics.
Ò Gangrene of the lower extremities, as a result
of advanced vascular disease is almost about
100 times more common in diabetics than the
general population
Ò Hyaline atherosclerosis(HA)
Ò This takes the form of an amorphous,
hyaline thickening of the wall of arterioles,
which causes narrowing of the lumen.
Ò It is a vascular lesion associated with
Hypertension and is more prevalent and
more severe in diabetics than non-diabetics.
It may also be seen in elderly non-diabetics
without hypertension.
Ò Thus in diabetics, it is related not only to the
duration of the disease but also to the level
of blood pressure.
Ò Diabetic Microangiopathy
Ò One of the most consistent morphologic
features of diabetes is diffuse thickening of
basement membranes. The thickening is
most evident in the capillaries of the skin,
skeletal muscle, retina, renal glomeruli, and
renal medulla.
Ò Despite the increase in the thickness of
basement membranes, diabetic capillaries
tend to leak more plasma proteins than
normal capillaries.
Ò This microangiopathy underlies the
development of diabetic retinopathy,
nephropathy and some forms of neuropathy
DIABETIC NEPHROPATHY
Renal failure is second only to Myocardial
infection (MI) AS A CAUSE OF DEATH FROM
DIABETES.
Three lesions are encountered in diabetic
nephropathy
1. Glomerular lesions.
2. Renal vascular lesions, principally
arteriolosclerosis and
3. Pyelonephritis, including necrotizing
papillitis.
The most important glomerular lesions are:
Ò Capillary basement membrane thickening.
Ò The capillary basement membranes are
thickened throughout their entire length.
Ò DMS consists of a diffuse increase in
mesengial matrix and is always associated
with basement membrane thickening. It’s
seen in most diabetics of more than 10 years
duration.
Ò Ngs connotes a glomerular lesion made
distinctive by ball-like deposits of a laminated
matrix situated at the periphery of the
glomerulus.
Ò These nodules are PAS positive and usually
contain trapped mesengial cells.
Ò This change which is distinctive is called
Kinmelstiel-Wilson lesion after the
pathologists who described it.
Ò This lesion is seen in approximately 15-30%
of long-term diabetics.
Ò Diffuse mesengial sclerosis may be seen in
association with old age and hypertension
but Ngs is pathognonomic of diabetes
Ò Both the diffuse and nodular forms of
glomerular sclerosis induce sufficient
ischaemia to cause overall fine scarring to
the kidneys, marked by a finely granular
cortical surface.
Note
Ò Hyaline arteriosclerosis affects not only the
afferent but also the efferent arteriole.
Ò Such efferent arteriosclerosis is rarely, if
ever encountered in individuals who do not
have diabetes
Ò Pyelonephronitis is an acute or chronic
inflammation of the kidneys that usually
begins at the interstitial tissue and spreads
to affect the tubules.
Ò Pylonephritis is more common in diabetics
than in the general population and tends to
worsen the severity of diabetes.
Ò One special pattern of acute pyelonephritis,
necrotizing papillitis (papillary necrosis) is
much more prevalent in diabetics than non-
diabetics.
Diabetic Ocular complications
include
Ò [Link].
Ò [Link] formation.
Ò [Link].
Diabetic neuropathy include
Òperipheral neuropathy and
Ò Autonomic neuropathy e.g in the bladder.
PANCREATIC ENDOCRINE
NEOPLASMS
Tumors of islet cells; account for < 5% of pancreatic
neoplasms.
1. Often a component of MEN 1 along with parathyroid
hyperplasia and pituitary adenomas
Insulinomas present as episodic hypoglycemia with mental
status changes that are relieved by administration of
glucose.
Diagnosed by 4- serum glucose levels (usually < 50 mg/dL),
total insulin, and total C-peptide.
Gastrinomas present as treatment-resistant peptic ulcers
(Zollingcr-Ellison syndrome); ulcers may be multiple and
can extend into the jejunum.
Somatostatinomas present as achlorhydria (due to inhibition
of gastrin) and cholelithiasis with steatorrhea (due to
inhibition of cholecystokinin).
Vipomas secrete excessive vasoactive intestinal peptide
leading to watery diarrhea, hypokalemia, and achlorhydria.
INSULINOMA
Ò β-cell tumors (insulinomas) are the most
common of pancreatic endocrine
neoplasms, and may produce sufficient
insulin to induce clinically significant
hypoglycaemia
Ò Insulinomas are most often found within the
pancreas and are generally benign
Ò Most are solitary, although multiple tumours
may be encountered
Ò Bona fide carcinomas, making up only
about 10% of cases, are diagnosed on the
basis of local invasion and distant
metastases
Ò On rare occasions an insulinoma may arise
in ectopic pancreatic tissue. In such cases,
electron microscopy reveals the distinctive
granules of β-cells
Ò Deposition of amyloid is a characteristic
feature of many insulinomas
Ò Surgical removal of the tumour is usually
followed by prompt reversal of the
hypoglycaemia
ZOLLINGER-ELLISON SYNDROME
(GASTRINOMAS)
Ò Marked hypersecretion of gastrin due to gastrin-
producing tumours (gastrinomas).
Ò Likely arise in the duodenum and peripancreatic
soft tissues as in the pancreas (so-called
gastrinoma triangle)
Ò Zollinger and Ellison first called attention to the
association of pancreatic islet cell lesions,
hypersecretion of gastric acid and severe peptic
ulceration.
Ò Present in 90% to 95% of patients
Ò Gastrinomas arise in conjunction with other
endocrine tumours, as part of the MEN-1
syndrome in 25% of patients.
Ò In Zollinger-Ellison Syndrome,
hypergastrinaemia gives rise to extreme
gastric acid secretion, resulting in peptic
ulceration.
Ò The duodenal and gastric ulcers are often
multiple, and unresponsive to therapy
ADRENAL CORTEX
Composed of three layers that each secrete
distinct hormones.
1. Glomerulosa produces mineralocorticoids (e.g.,
aldosterone).
2. Fasciculata produces glucocorticoids (e.g.,
Cortisol).
3. Reticularis produces sex steroids (e.g.,
testosterone).
HYPERCORTISOLISM (CUSHING
SYNDROME)
Excess Cortisol
Ò Clinical features
1. Muscle weakness with thin
extremities—Cortisol breaks down muscle for
gluconeogenesis.
2. Moon fades, buffalo bump, and truncal
obesity—High insulin {due to high glucose)
increases storage of fat,
3. Abdominal striae—due to impaired synthesis of
collagen with thinning of skin
4. Hypertension
5. Osteoporosis
6. Immune suppression
Diagnosis is made by increased 24-hour urine
Cortisol levels.
ÒA patient with Cushing
syndrome
demonstrating central
obesity, “moon facies,”
and abdominal striae
Ò Causes include
1. Exogenous corticosteroids—Ieads to
biIateraI adrenal atrophy; steroids suppress
ACTH secretion (negative feedback).
2. Primary adrenal adenoma, hyperplasia, or
carcinoma—leads to atrophy of the
uninvolved adrenal gland
3. ACTH-secreting pituitary adenoma—leads to
bilateral adrenal hyperplasia
4. Paraneoplas tic ACTH secretion (e.g., small
cell carcinoma of the lung)—leads to bilateral
adrenal hyperplasia
Ò High-dose dexamethasone (Cortisol analog)
suppresses ACTH production by a pituitary
adenoma (Cortisol levels decrease), but fails
to suppress ectopic ACTH production by a
small cell lung carcinoma (Cortisol levels
remain high).
HYPER ALDOSTERONISM (CONN
SYNDROME)
Excess aldosterone
Presents as hypertension with
hypernatremia, hypokalemia, and
metabolic alkalosis
1. Aldosterone increases sodium
absorptioniild secretion of potassium and
hydrogen ions (distal tubules and collecting
duct).
2. Increased absorption of sodium expands
plasma volume leading to hypertension.
HYPER ALDOSTERONISM (CONN
SYNDROME)
Primary hyperaldosteronism is most
commonly due to an adrenal adenoma;
Sporadic adrenal hyperplasia and Adrenal
carcinoma are less common causes.
Characterized by high aldosterone and low
renin (high blood pressure downregulates
renin via negative feedback).
Secondary hyperaldosteronism is seen with
activation of the renin-angiotensin system
(e.g., renovascular hypertension or CHE).
Characterized by high aldosterone and high
renin
CONGENITAL ADRENAL HYPERPLASIA
Excess sex steroids with hyperplasia of both
adrenal glands
Inherited 21-hydroxylase deficiency is the most
common cause.
1. 21-hydroxylase is required for the
production of aldosteroiieand
corticosteroids.
2. In enzyme deficiency, steroidogenesis is
predominantly shunted toward sex steroid
production (which does not require 21 -
hydroxylase).
3. Deficiency of Cortisol leads to increased ACTH
secretion (lack of negative feedback), which
results in bilateral adrenal hyperplasia.
CONGENITAL ADRENAL HYPERPLASIA
Clinical features include
1. Salt wasting with hyponatremia,
hyperkalemia, and hypovolemia due to lack
of aldosterone.
2. Life-threatening hypotension due to lack of
Cortisol.
3. Clitoral enlargement (females) or precocious
puberty (males) due to excess androgens
ADRENAL INSUFFICIENCY
Lack of adrenal hormones
Acute insufficiency may arise with
Waterhouse-Friderichsen syndrome.
1. Characterized by hemorrhagic necrosis of
the adrenal glands classically due to DIC in
young children with N meningitidis infection
2. Lack of Cortisol exacerbates hypotension,
often leading to death.
CHRONIC INSUFFICIENCY (ADDISON
DISEASE)
Is due to progressive destruction of the adrenal
glands.
Common causes include autoimmune destruction
(most common cause in the West), TB (most
common cause in the developing world), and
metastatic carcinoma [e.g., arising from lung),
Clinical features include hypotension,
hyponatremia, hypovolemia, hyperkalemia,
weakness, hyperpigmentation (increased
ACTH by-products stimulate melanocytic
production of pigment), vomiting, and diarrhea.
ADRENAL MEDULLA
Composed of neural crest-derived chromaffin
cells
Main physiologic source of catecholamines
[epinephrine and norepinephrine).
PHEOCHROMOCYTOMA
Tumor of chromaffin cells.
Clinical features are due to increased serum
catecholamines.
Episodic hypertension, headache, palpitations,
tachycardia, and sweating
Diagnosed by increased serum metanephrines
and increased 24-hour urine metanephrines
and vanillylmandelic acid
Treatment is surgical excision.
1. Catecholamines may leak into the bloodstream
upon manipulation of the tumor.
2. Phenoxybenzamine (irreversible a-blocker) is
administered periop era lively to prevent a
hypertensive crisis.
Often follows the 'rule of 10s:' 10% bilateral, 10%
familial, 10% malignant, and 10% located
outside of the adrenal medulla (e.g., bladder
wall or organ of Zuckerkandl at the inferior
mesenteric ariery root)
Associated with MEN 2A and 2B, von Hippel-
Iindau disease, and neurofibromatosis type 1.
MULTIPLE ENDOCRINE
NEOPLASIA(MEN)
Ò The MEN syndromes are a group of inherited
diseases resulting in proliferative lesions
(hyperplasia, adenomas, and carcinomas) of
multiple endocrine organs
Ò MEN-1, or Wermer syndrome, is a rare heritable
disorder with a prevalence of about 2 per 100,000.
Ò MEN-1 is characterized by abnormalities
involving the parathyroid, pancreas, and
pituitary glands; thus the mnemonic device, the
3Ps
Ò The duodenum is the most common site of
gastrinomas in individuals with MEN-1 and
synchronous duodenal and pancreatic tumours
may be present in the same individual
Ò In addition, carcinoid tumours, thyroid and
adrenocortical adenomas, and lipomas are
more frequent than in the general population
Ò MEN-2 is subclassified into three distinct
syndromes:
MEN-2A
MEN-2B, and
Familial medullary thyroid cancer
Ò MEN-2A, or Sipple syndrome, is
characterized by pheochromocytoma,
medullary carcinoma of the thyroid, and
parathyroid hyperplasia
Ò MEN-2B has significant clinical overlap with
MEN-2A
Ò Patients develop medullary thyroid
carcinomas, which are usually multifocal and
more aggressive than in MEN-2A, and
pheochromocytomas
Ò However, unlike in MEN-2A, primary
hyperparathyroidism is NOT present
PINEAL GLAND
Ò It is a minute, pinecone-shaped organ (hence
its name), weighing 100 to 180 mg and lying
between the superior colliculi at the base of the
brain
Ò It is composed of a loose, neuroglial stroma
enclosing nests of epithelial-appearing
pineocytes, cells with photosensory and
neuroendocrine functions (hence the
designation of the pineal gland as the “third eye”
Ò The principal secretory product of the pineal
gland is melatonin, which is involved in the
control of circadian rhythms, including the
sleep-wake cycle; hence the popular use of
melatonin for the treatment of jet lag
PINEOLOMAS
Ò These neoplasms are divided into two
categories, pineoblastomas and
pineocytomas, based on their level of
differentiation, which, in turn, correlates with
their aggressiveness
Ò These tumors are rare
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