Endocrine Day 2 template

Hyperaldosteronism Cushing Syndrome Adrenal insufficiency

Cause Increased secretion from -Exogenous Primary (Addison
adrenal gland corticosteroids (most Disease): adrenal
common) atrophy or destruction
Primary: via autoimmune
-Bilateral adrenal hyperplasia -Primary adrenal adrenalitis (developed
-Adrenal adenoma (Conn adenoma/hyperplasi areas) or TB (developing
Syndrome) a/carcinoma areas)

Secondary: -Cushing DISEASE

-Renovascular HTN (ACTH secreting dec gland function→
-Juxtaglomerular cell tumors pituitary adenoma) dec cortisol →
-Edema secondary to heart dec aldosterone →
failure, cirrhosis, nephrotic -Paraneoplastic signs/symptoms
syndrome ACTH secretion
(small cell lung Secondary: low pituitary
cancer, bronchial ACTH secretion
carcinoids)
Tertiary: low
hypothalamic CRH
secretion ( abrupt
cessation of chronic
steroid therapy)

Hormonal Both: High Aldosterone
abnormality
Primary: Low Renin
Signs & -Hypertension (Treatment
symptoms resistant in primary)
-Edema (secondary)
Acute
(adrenal/addisonian)
crisis: acute stressors
that inc steroid
requirements ( infection)
in pts w/ pre-existing
adrenal insufficiency or
on steroid therapy
High cortisol Low glucocorticoids +/−
mineralocorticoids
Cholesterol high -weakness
Urinary free cortisol -fatigue
high -orthostatic hypotension
Skin changes (hyponatremic volume
(thinning, striae) contraction)
Hypertension -muscle aches
 Immunosuppression -weight loss
Neoplasm (cause) -GI disturbances
Growth restriction -Sugar and/or salt
(kids) cravings
Sugar high/insulin -hyperkalemia, -
resistance metabolic acidosis
-skin/mucosal
Amenorrhea hyperpigmentation
Moon facies (primary only):
Buffalo hump (inc melanin synthesis
Osteoporosis due to inc MSH/
Truncal obesity byproduct of POMC
Hirsutism cleavage)

Acute crisis:
-acute abdomen,
nausea, vomiting,
altered mental status,
shock.

Waterhouse-
Friderichsen syndrome:
bilateral adrenal
hemorrhage (often
meningococcemia)
-acute adrenal
insufficiency
-fever
-petechiae
-sepsis
Labs -Dec or nml K+ -24hr urine free
-Metabolic alkalosis cortisol or late night
salivary cortisol
+
-Dexamethasone
suppression test
Treatment Spironolactone Ketoconazole or glucocorticoid +/−
surgical excision of mineralocorticoid
tumor replacement

Cushing’s diagnostic test

Adrenal insufficiency test
Neuroendocrine tumors
What are these? Heterogenous group of neoplasms originating from neuroendocrine
cells ( traits similar to nerve cells and hormone- producing cells)
Where do they GI system ,adrenals, pancreas, thyroid and lungs
occur?
What are their amine precursor uptake decarboxylase
secretory products?
Treatment? surgical resection and somatostatin analogues
Pheochromocytoma Neuroblastoma Carcinoid syndrome
What is it? Most Common tumor Most Common Secrete serotonin 5-T
of the adrenal tumor of the in the intestine or
medulla in adults. adrenal medulla in lung
children, usually < 4 reaches the systemic
yo. circulation
Risk factors
Derived from? Chromaffin cells Neural crest cells, Arise from
( arise from neural Occurs anywhere neuroendocrine cells
crest) along the and secrete 5-HT
sympathetic chain

Signs & symptoms Secrete epinephrine, Abdominal Cutaneous flushing,

norepinephrine and distention and a diarrhea,
dopamine, cause firm, irregular mass bronchospasm,
episodic that can cross the wheezing, (right-
hypertension. midline. sided valvular heart
disease
Secrete EPO→ opsoclonus-
Polycythemia myoclonus
syndrome

Less likely to
develop
hypertension
Labs Increase Increase
catecholamines and homovanillic acid
metanephrines in and
urine and plasma vanillylmandelic
(homovanillic acid , acid in urine
vanillylmandelic acid)
Treatment Irreversible alpha- Surgical resection
antagonists followed (somatostatin)
by beta blockers Octreotide, Telotristat
prior to tumor
resection.
Genetic associations Germline mutations: Amplification of N-
NF-1, VHL, RET myc oncogene
(MEN2A, 2B)

Histology Homer- Wright Prominent rosettes

rosettes Chromogranin A (+),
(neuroblasts synaptophysin (+)
surrounding a
central lumen

Bombesin and
NSE(+)
 Glucagonoma Insulinoma Somatostatinoma
Tumor of what? pancreatic α cells pancreatic β cells pancreatic δ cells
Overproduction of glucagon insulin somatostatin
what?
Signs & symptoms Presents with 6 D’s: Whipple triad: a) low -> decreased
dermatitis (necrolytic blood glucose, b) secretin, CCK,
migratory erythema), hypoglycemia glucagon, insulin,
diabetes symptoms (eg, gastrin, gastric
(hyperglycemia), lethargy, syncope, inhibitory peptide
DVT, diplopia), c) (GIP).
declining weight, symptoms resolve
depression, diarrhea. after normalization diabetes/ glucose
of plasma glucose intolerance,
levels steatorrhea,
gallstones,
dec. blood glucose achlorhydria
and inc. C-peptide
levels (vs exogenous
insulin use)
Treatment octreotide, surgical surgical resection surgical resection,
resection somatostatin analogs
(eg, octreotide)
Associations ∼ 10% cases
associated w/ MEN 1
syndrome

Zollinger Ellison syndrome

Tumor of what? duodenum or pancreas
Overproduction of Gastrin (gastrinoma)
what?
Signs & symptoms recurrent ulcers in duodenum and jejunum, abdominal pain (peptic
ulcer disease, distal ulcers), diarrhea (malabsorption)

Positive secretin stimulation test: increased gastrin levels after

administration of secretin, which normally inhibits gastrin release
Treatment PPIs, octreotide, surgical resection for nonmetastatic, chemo for
metastatic
Associations MEN 1

Hypothyroidism
Metabolic Cold Intolerance,decreased
sweating, weight
gain( decreased basal
metabolic rate >> decreased
calorigenesis), hyponatremia
(decreased free water
clearance)
Skin/hair Dry, cool skin (due to blood
flow); coarse, brittle hair;
diffuse alopecia; brittle nails;
puffy facies generalized non
pitting edema (myxedema)
due to increased GAGs in
interstitial spaces>> increased
osmotic pressure >> increased
water retention
Eye Periorbital Edema
GI Constipation (decreased GI
motility), appetite
MSK Hypothyroidmyopathy
(proximal weakness,
increased CK), carpal tunnel
syndrome,myoedema(small
Hyperthyroidism
Heat intolerance, increased
sweating, weight loss
(increased synthesis of Na+-
K+ATPase basal >> basal
metabolic rate>> increased
calorigenesis
Warm, moist skin (due to
vasodilation); fine hair;
onycholysis (A); pretibial
myxedema in Graves disease
Ophthalmopathy in Graves
disease (including periorbital
edema, exophthalmos), lid
lag/retraction (increased
sympathetic stimulation of
levator palpebrae superioris
and superior tarsal muscle)
Hyperdefecation/
diarrhea( GImotility),
appetite
Thyrotoxic Myopathy
(proximal weakness, normal
CK),osteoporosis/ increased
fracture rate(T3 Directly
 lump rising on the surface of a Stimulates Bone Resorption)
muscle when struck with a
hammer)
Repro Abnormal Uterine Bleeding,
decreased libido,infertility
Neuropsych Hypoactivity, lethargy,
fatigue, weakness, depressed restlessness,anxiety,
mood, decreased reflexes
(delayed/slow relaxing)
Cardio Bradycardia, dyspnea on
exertion ( decreased cardiac
output)
Labs
Hypothyroidism Hashimoto thyroiditis Postpartum
thyroiditis
Abnormal Uterine Bleeding,
gynecomastia, decreased
libido,infertility
Hyperactivity,
insomnia, fine tremors (due
to increased β-adrenergic
activity), increased
reflexes(brisk)
Tachycardia, palpitations,
dyspnea, arrhythmias
(eg,atrial fibrillation), chest
pain and systolic HTN due to
increased number and
sensitivity of β-adrenergic
receptors, increased
expression of cardiac
sarcolemmal ATPase and
expression of
phospholamban
Subacute
granulomatous
thyroiditis
(de Quervain)
Risk factors Also called chronic Mild, self limited Often preceded by a
autoimmune variant of Hashimoto viral infection.
thyroiditis. Most thyroiditis arising < 1 Usually a self limited
common cause of year after delivery. disease. Natural
hypothyroidism in history: transient
iodine sufficient hyperthyroidism --->
regions. euthyroid state --->
hypothyroidism
Immuno association HLA-DR3
Antibodies antithyroglobulin
antibodies
Histopath Hurthle cells (image / Granulomatous
A), lymphoid inflammation (image
aggregates with C)
germinal centers
(image B)
Clinical symptoms Moderately enlarged, / Jaw pain, very tender
nontender thyroid. thyroid
May be preceded by
transient
hyperthyroid state
(“Hashitoxicosis”)
due to follicular
rupture and thyroid
hormone release
Labs Positive antithyroid / Increase in ESR
peroxidase
(antimicrosomal)
Radioactive iodine / Low
uptake

Hypothyroidism Congenital Riedel thyroiditis

Hypothyroidism (cretinism)
Risk factors Most commonly caused by
thyroid dysgenesis or
dyshormonogenesis in
iodine-sufficient regions
Mechanism abnormal thyroid gland
development; eg, agenesis,
hypoplasia, ectopy.
abnormal thyroid hormone
synthesis; eg, mutations in
Also called invasive fibrous
thyroiditis
May be part of IgG4-related
disease (eg, autoimmune
pancreatitis, retroperitoneal
fibrosis, noninfectious
aortitis). Hypothyroidism
 thyroid peroxidase
Histopath Protuberant tongue (image
F), puffy faced child (image E)
Clinical symptoms 6 P’s: pot bellied, pale, puffy-
faced child with protruding
umbilicus, protuberant
tongue and poor brain
development.
occurs in ⅓ of patients.
Fibrosis may extend to local
structures (trachea,
esophagus), mimicking
anaplastic carcinoma.
Thyroid replaced by fibrous
tissue and inflammatory
infiltrate (Image D)
Slowly enlarging, hard (rock-
like), fixed, nontender
thyroid.

Wolff-Chaikoff effect Jod-Basedow phenomenon

Is an effective means of rejecting the large An iodide induced hyperthyroidism. It's a rare
quantities of iodide and therefore preventing cause of thyrotoxicosis typically seen after
the thyroid from synthesizing large quantities the administration of exogenous iodine.
of thyroid hormones.

Hyperthyroidism Graves disease Toxic multinodular Thyroid storm

 goiter
Risk factors stress, pregnancy hyperthyroidism hyperthyroidism is
incompletely
treated/ untreated
and then significantly
worsens in the
setting of acute
stress such as
infection, trauma,
surgery
Immuno association HLA-DR3 and HLA-B8
Antibodies Thyroid-stimulating
immunoglobulin

Histopath tall, crowded Focal patches of

follicular epithelial hyperfunctioning
cells; scalloped follicular cells
colloid. distended with
colloid working
independently
Clinical symptoms - pretibial myxedema - heat intolerance - agitation
- orbital fibroblast - muscle - delirium
- exophthalmos weakness/wasting - fever
- hyperactivity -diarrhea
- fatigue - coma
- tremor - tachyarrhythmia
- irritability
- weight loss
- osteoporosis
- increased appetite

Labs decrease TSH and increased release of increased LFT

increased T3 & T4 T3 and T4
Radioactive iodine increased hot and cold nodules
uptake

pg. 351 Thyroid adenoma Thyroid cancer

 Benign or Benign Malignant
malignant?
Histology follicular; absence of capsular or
vascular invasion (unlike follicular
carcinoma).
Diagnosed with fine needle aspiration
what?
Complications of - hypocalcemia- due to removal of
surgery? parathyroid glands

- transection of recurrent laryngeal

nerve during ligation of inferior
thyroid artery (leads to dysphagia
and dysphonia [hoarseness])

- injury to the external branch of the

superior laryngeal nerve during
ligation of superior thyroid vascular
pedicle (may lead to loss of tenor
usually noticeable in professional
voice users).

Thyroid cancer Histopath Genetics Associations Prognosis

Papillary ○ Empty-appearing nuclei ↑ risk with: Palpable lymph nodes Good
carcinoma with central clearing
○ “Orphan Annie” eyes ● RET/PTC Childhood irradiation (to 5-year
Most Prevalent ○ rearrangements head and neck) survival rate
(thyroid cancer) ● psamMoma bodies ⇒ > 90%
○ “Papi and Moma adopted ● BRAF mutations
Orphan Annie”

● nuclear grooves

Follicular Uniform follicles ● RAS mutation Follicular adenoma “Good”

carcinoma (hematogenous spread is ● Adenoma does not invade (5-year
common) ● PAX8-PPAR-γ thyroid capsule &/or survival rate
rearrangement vasculature ⇒ 50–70%)
● Carcinoma invades

BUT

Fine needle aspiration

cannot distinguish btw
adenoma/carcinoma
Medullary with Congo red → sheets MEN2A and 2B Parafollicular “C cells” Coin-toss
carcinoma of polygonal cells in an (RET mutations)
amyloid stroma or Produces Calcitonin → (5-year
familial medullary Lowers serum calcium survival rate
carcinoma ⇒ 50%)
Amyloid = protein deposits
&&
Calcitonin = peptide ⇒⇒
Amyloid deposits in thyroid
Anaplastic Undifferentiated cell; TP53 mutation Occurs in elderly Very Poor
carcinoma prognosis
No papilla, TP53 gene → Rapidly enlarging neck mass
No follicles, produces → p53, → compressive symptoms
activates p21, blocks
No amyloid (dyspnea, dysphagia, 5-year
G1 → S phase
hoarseness) → survival rate
⇒ 5–14%

Similar presentation to →
Riedel thyroiditis (“rock-like”,
slowly enlarging, & younger
pt)
Hypoparathyroidism
What is it due to? Injury to
● parathyroid glands or their blood supply (usually during surgery),
● autoimmune destruction, or
● DiGeorge syndrome.

Clinical findings? ■ Tetany,

■ Hypocalcemia,
■ Hyperphosphatemia
■ Chvostek sign—tapping of facial nerve (tap the Cheek) → contraction of
facial muscles.
■ Trousseau sign—occlusion of brachial artery with BP cuff (cuff the
Triceps) → carpal spasm

Pseudohypoparathyroidism type 1A Pseudopseudohypoparathyroidism

Inheritance autosomal dominant

Maternally or maternally paternally
paternally
inherited?
Physical exam Albright hereditary osteodystrophy (shortened 4th/5th digits, short stature,
findings round face, subcutaneous calcifications, developmental delay)

end-organ (kidney and bone) end-organs are

resistance to PTH without resistance to PTH
Labs Increased: normal:
PTH, Ca2+, PO43– PTH, Ca2+, PO43–.

Hyperparathyroidis Primary Secondary Tertiary

m Hyperparathyroidism hyperparathyroidism hyperparathyroidism
What is it due to? Parathyroid adenoma 2° hyperplasia due to Refractory
or hyperplasia ↓Ca2+ absorption (autonomous)
and/or ↑PO43−, hyperparathyroidism
most often in chronic resulting from
kidney disease chronic kidney
disease. ↑↑ PTH, ↑
Ca2+.

Clinical symptoms? Mostly asymptomatic

+/- bone pain,
weakness,
constipation,
abdominal/plank
pain (kidney stones,
acute pancreatitis),
neuropsychiatric
disturbances
“bones, groans,
psychiatric
overtones”
Labs Hypercalcemia, Hypovitaminosis D
hypercalciuria, and
polyuria, Hyperphosphatemia
hypophosphatemia, → ↑Ca2+).
↑PTH, ↑ALP,
↑urinary cAMP Hypocalcemia,
hyperphosphatemia
in chronic kidney
disease (vs
hypophosphatemia
with most other
causes), ↑ ALP, ↑
PTH.

Osteitis fibrosa What is it? – cystic bone spaces filled with brown fibrous tissue
cystica Due to what? - ↑ PTH, classically associated with 1° (but also seen
with 2°) hyperparathyroidism.
Renal osteodystrophy What is it? – Kidney disease that leads to bone lesions
Due to what? - (Pathogenesis) Renal disease → 2° and 3°
hyperparathyroidism → bone lesions

Familial hypocalciuric What is it? – (FHH) is an inherited disorder that causes abnormally
hypercalcemia high levels of calcium in the blood (hypercalcemia) and low to
moderate levels of calcium in urine (hypocalciuric)
Due to what? – Defective G-coupled Ca2+-sensing receptors in
multiple tissue
Labs? - Hypercalcemia and hypocalciuria with normal to ↑PTH levels.

Hypopituitarism Sheehan syndrome Empty sella Pituitary apoplexy

syndrome
What is it? ischemic infarct of atrophy or sudden hemorrhage
pituitary following compression of of pituitary gland,
postpartum bleeding; pituitary (which lies often in the presence
pregnancy induced in the sella turcica), of an existing
pituitary growth   often idiopathic, pituitary adenoma.
 leading to increased common in obese Usually presents with
  susceptibility to females; associated sudden onset severe
hypoperfusion. with idiopathic headache, visual
Usually presents with intracranial impairment (eg,
failure to hypertension bitemporal
lactate, absent hemianopia, diplopia
menstruation, cold due to CN III palsy),
intolerance and features of
hypopituitarism
Treatment hormone replacement therapy (corticosteroids, thyroxine, sex
steroids, human growth
hormone)

Acromegaly

Risk factors
Mechanism Excess GH in adults. Typically caused by pituitary adenoma.

Sign and symptoms Large tongue with deep furrows, deep voice,
large hands and feet, coarsening of facial
features with aging A , frontal bossing,
diaphoresis (excessive sweating), impaired
glucose tolerance (insulin resistance),
hypertension. increased  risk of colorectal polyps and
cancer.
Diagnostic tests increased serum IGF-1; failure to suppress serum GH
following oral glucose tolerance test; pituitary
mass seen on brain MRI.

Treatment Pituitary adenoma resection. If not cured,

treat with octreotide (somatostatin analog),
pegvisomant (GH receptor antagonist), or
dopamine agonists (eg, cabergoline).

Complications  increased GH in children  leads to gigantism ( increased linear

bone
growth). HF most common cause of death.

Clinical symptoms
Complication of Type 1
DM
Complication of Type 2
DM
Diabetes Mellitus: Acute Manifestations
● Polydipsia, polyuria, polyphagia, weight loss
● Diabetic ketoacidosis
● Hyperosmolar hyperglycemic state

Diabetes Mellitus: Chronic Complications

Nonenzymatic glycation
Examples:
● Small vessel disease (diffuse thickening of
basement membrane) → retinopathy
(hemorrhage, exudates, microaneurysms,
vessel proliferation), glaucoma,
nephropathy; nodular glomerulosclerosis
Osmotic damage
Examples:
● Sorbitol accumulation in organs w/ aldose
reductase and ↓/absent sorbitol
dehydrogenase →
○ Neuropathy (motor, sensory - glove &
stocking distribution, autonomic
 → progressive proteinuria (initially degeneration)
microalbuminuria; ACEi/ARBs = ○ Cataracts
renoprotective) & arteriosclerosis (causing
HTN) → CKD
● Large vessel atherosclerosis, CAD,
peripheral vascular occlusive disease,
gangrene → limb loss, cerebrovascular
disease; MI = most common cause of death

Diabetes Mellitus: Diagnosis

Test Diagnostic criteria Notes
● HbA1c ● ≥ 6.5% ● Reflects average blood glucose over
past 3 months

● Fasting plasma ● ≥ 126 mg/dL ● Fasting > 8 hours

glucose
● 2-hour oral ● ≥ 200 mg/dL ● 2 hours after consumption of 75 g of
glucose glucose in water
tolerance test
Insulin deficiency or severe insulin insensitivity
 Type 1 vs Type 2 Diabetes Mellitus
Type 1 Type 2
Mechanism ● Autoimmune T-cell-mediated ● ↑ insulin resistance, progressive
destruction of β-cells pancreatic β-cell failure
○ Ex: due to presence of glutamic
acid decarboxylase antibodies
Age ● < 30 y/o ● > 40 y/o
Obesity ● No ● Yes
Association with ● Yes ● No
HLA ○ HLA-DR4 & -DR3
“4-3 = type 1”
Glucose ● Severe ● Mild to moderate
intolerance
Insulin sensitivity ● High ● Low
Ketoacidosis ● Common ● Rare
Histology ● Islet leukocyte infiltrate ● Islet amyloid polypeptide (IAPP)
deposits

Diabetic ketoacidosis Hyperosmolar hyperglycemic state

Insulin ● Absent
Ketones ● Present
Mechanism ● Insulin non compliance or ↑
requirements from ↑ stress (ex:
infection) → excess fat breakdown & ↑
ketogenesis from ↑ free fatty acids →
ketone bodies (β-hydroxybutyrate >>
acetoacetate)
Signs & symptoms “DKA is Deadly”
● Delirium/psychosis
● Kussmaul respirations (rapid, deep
breathing)
● Abdominal pain/nausea/vomiting
● Dehydration
● Fruity breath odor (due to exhaled
acetone)
Labs ● Hyperglycemia, ↑ H+, ↓ HCO3- (↑
anion gap metabolic acidosis), ↑ urine
& blood ketones, leukocytosis
● Normal/↑ serum K+ but ↓
intracellular K+ (due to intracellular
shift from ↓ insulin & acidosis)
● Osmotic diuresis → ↑ K+ loss in urine
→ total body K+ depletion
● Present
● Absent
● Profound hyperglycemia → excessive
osmotic diuresis → dehydration & ↑
serum osmolality → HHS
○ Classically seen in elderly DMII
patients w/ limited ability to drink
● Thirst
● Polyuria
● Lethargy
● Focal neurologic deficits
● Seizures
● Hyperglycemia (often >600 mg/dL), ↑
serum osmolality (>320 mOsm/kg),
normal pH, no ketones
● Normal/↑ serum K+, ↓ intracellular
K+
Complications ● Life-threatening mucormycosis,
cerebral edema, cardiac arrhythmias,
HF
Treatment ● IV fluids, IV insulin, K+ (to replete
intracellular stores) +/- glucose to
prevent hypoglycemia
● Can progress to coma & death if
untreated
● IV fluids, IV insulin, & K+ (to replete
intracellular stores)

Multiple MEN 1 MEN 2A MEN 2B aka 3

Endocrine “3P” “2P + 1M” aka “1P + 2M”
Neoplasias
“Sipple
Syndrome”
What tumors? -Pituitary Tumors -Parathyroid -Pheochromocytoma
● Prolactin or GH Hyperplasia
-Pancreatic Endocrine -Medullary Thyroid
Tumor -Pheochromocytoma Carcinoma
● Zollinger-Ellison → secretes
Syndrome catecholamines -Mucosal Neuromas
● Insulinoma (oral/intestinal
● VIPomas NOTE: Required ganglioneuromatosis
● Glucagonoma Prophylactic )
-Parathyroid Adenomas Thyroidectomy

-Medullary Thyroid
Carcinoma →
Neoplasm of
Parafollicular C cells,
Secretes Calcitonin
Genetic -Mutation in MEN1 -Mutation in RET -Mutation in RET
association (menin - tumor gene (codes for gene
suppressor, receptor tyrosine -Associated with
chromosome 11) kinase) Marfanoid Habitus

NOTE: Angiofibromas,
Collagenomas,
Meningiomas