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endocrine

PITUITARY HORMONES
Anterior pituitary :
Prolactin
Growth hormone
TSH
FSH\LH
ACTH
PITUITARY HORMONES
Posterior pituitary :
Anti-Diuretic Hormone (ADH).
Oxytocin.
PROLACTIN
Source : anterior pituitary (lactotrophes).
Function :
stimulates milk production in breast.
Inhibits ovulation in females (by inhibiting
GnRH).
Inhibits Spermatogenesis in males (by
inhibiting GnRH).
PROLACTIN
TRHprolactin secretion (eg, in 1 or 2
hypothyroidism).
PROLACTIN
Dopamine agonists (eg, bromocriptine) inhibit
prolactin secretion and can be used in
treatment of prolactinoma.
Dopamine antagonists (eg, most
antipsychotics) and estrogens (eg, OCPs,
pregnancy) stimulate prolactin secretion.
Prolactin-related disorders
Hyper-prolactinemia : high level of prolactin in
the blood .
Causes :
Pregnency.
Chest wall stimulation
Renal failure
Hypothyroidism
Cutting of the stalk .
Drugs : dopamine antagonist.
Pituitary adenoma.
PROLACTINOMA
Benign , prolactin-producing pituitary
adenoma originates from lactotrophes.
Presentation :
Mass effect : headache , bitemporal
hemianopia , hypopituitarism.
Physiological effect : amenorrhea
(osteoporosis) , galactorrhea (female only) ,
decreased libido , infertility , gynecomastia.
PROLACTINOMA
Dx :
High level of prolactin
Exclude pregnancy and other secondary
causes.
MRI.
PROLACTINOMA
Treatment : dopamine agonist or
transsphenoidal resection.
GROWTH HORMONE
(SOMATOTROPIN)
SOURCE : anterior pituitary
Stimulates linear growth and muscle mass
through IGF-1 (somatomedin C) secretion by
liver.
insulin resistance (diabetogenic).
GROWTH HORMONE
(SOMATOTROPIN)
Released in pulses in response to growth
hormonereleasing hormone (GHRH).
Secretion
is increased during exercise, deep
sleep, puberty, hypoglycemia.
Secretion inhibited by glucose and
somatostatin release via negative feedback by
somatomedin.
GHRH analogue (tesamorelin) hiv-
associated lipodystrophy.
GROWTH HORMONE
(SOMATOTROPIN)

Hiv-associated lipodystrophy
GROWTH HORMONE RELATED
DISORDERS
Absence of GH dwarfism .
Excessive GH : acromegaly , gigantism.
ACROMEGALY
Mostly due to pituitary adenoma.
Presentation : large tongue with deep furrows
OSA , deep voice , large hands and feet ,
coarse facial features , prognathism, frontal
bossing, diaphoresis (excessive sweating)
oily skin .
DM ?
Increased risk of colorectal polyps and cancer.
ACROMEGALY
ACROMEGALY
ACROMEGALY
GIGANTISM
GH in children gigantism (
linear bone growth).
ACROMEGALY AND GIGANTISM
Death is due to heart failure.
ACROMEGALY AND GIGANTISM
Diagnosis :
serum IGF-1
Failure to supress GH after OGTT.
Brain MRI.
ACROMEGALY AND GIGANTISM
Treatment :
Resection of pituitary adenoma.
If not cured : octreotide or pegvisomant.
DWARFISM
Due to GH defeciency or GH receptor
deficiency (laron dwarfism)
LARON dwarfism
Defective growth hormone receptors
decreased linear growth.
high GH, low IGF-1.
Clinical features include short height, small
head circumference, characteristic facies with
saddle nose and prominent forehead, delayed
skeletal maturation, small genitalia.
LARON DWARFISM
LARON DWARFISM
Treatment :
Synthetic IGF-1
CALCIUM HOMEOSTASIS
Exists in 3 forms :
Ionized form (active form) 45%
Bound to albumin 40%
Bound to anions (PO4-) 15%
CALCIUM HOMEOSTASIS
Total calcium level is affected by albumin level
, every decrease in albumin by 1 leads to
decrease in total calcium by 0.8.

Always look at albumin level in any patient


with hypocalcaemia.
CALCIUM HOMEOSTASIS
In renal failure accumulation of PO4-
hypocalcemia.
CALCIUM HOMEOSTASIS
increase in pH increases affinity of albumin
increases negative charge) to bind Ca2+
(
hypocalcemia.

Hyperventilation ?
CALCIUM HOMEOSTASIS
Affected by 3 factores :
Vit. D
Parathyroid.
Calcitonin.
Vitamin D (cholecalciferol)
D3 from exposure of skin to sun, ingestion of
fish and plants.
D2 from ingestion of plants, fungi, yeasts.
Both converted to 25-OH in liver and to 1,25-
(OH)2 (active form) in kidney , or 24,25-(OH)2
which is Inactive.
Vitamin D (cholecalciferol)
increases absorption of dietary Ca2+ and
PO4 from GI and kidneys.
Enhances bone mineralization\resporption.
Increases resorption of the old bone to build
new one.
Vitamin D (cholecalciferol)
Regulation :
high PTH
low Ca2+
low PO4-
increase 1,25-(OH)2 production.
1,25-(OH)2 feedback inhibits its own
production.
Vitamin D (cholecalciferol)
Deficiency rickets in kids, osteomalacia in
adults.
PARATHYROID HORMONE (PTH)
Controls Min-to-min calcium level FAST.
PARATHYROID HORMONE (PTH)
increasesbone resorption of Ca2+ and PO4-.

increases kidney reabsorption of Ca2+ in distal
convoluted tubule.
d
ecreases reabsorption of PO4 in proximal
convoluted tubule.

increases 1,25-(OH)2 D3 (calcitriol) production
by stimulating kidney 1-hydroxylase in
proximal convoluted tubule.
PARATHYROID HORMONE (PTH)
PTH increases serum Ca2+, decreases
serum (PO4), increases urine (PO4 ),
increases urine cAMP.
PARATHYROID HORMONE (PTH)
increasesRANK-L (receptor activator of NH-B
ligand) secreted by osteoblasts and
osteocytes.
Binds RANK (receptor) on osteoclasts and
their precursors to stimulate osteoclasts and
Ca2+bone resorption (high alkaline
phosphatase)
PARATHYROID HORMONE (PTH)
Intermittent PTH release can also stimulate
bone formation.
Teriparatide : PTH analogue.
PARATHYROID HORMONE (PTH)
PTH-related peptide (PTHrP) functions like
PTH and is commonly increased in
malignancies (eg, squamous cell carcinoma of
the lung, renal cell carcinoma)
paraneoplastic hypercalcemia.
PARATHYROID HORMONE (PTH)
Regulation :
lowserum Ca2+ increasesPTH secretion.
highserum PO4 increases PTH secretion.
low serum Mg2+ increases PTH secretion.
very low serum Mg2+ d
ecreasesPTH
secretion.
PARATHYROID HORMONE (PTH)
Common causes of low Mg2+ include
diarrhea,aminoglycosides, diuretics, alcohol
abuse DADA
CALCITONIN
Source :Parafollicular cells (C cells) of thyroid.
Function :
decreases bone resorption of Ca2+.

regulation : high serum Ca2+ induces
calcitonin secretion Not important in
normal Ca2+ homeostasis.
Pt. with hypocalcaemia ??
PTH-related Disorders
HYPOPARATHYROIDISM
Due to accidental surgical excision of
parathyroid glands, autoimmune destruction,
or DiGeorge syndrome.
HYPOPARATHYROIDISM
Presentation : Sx of hypocalcemia cramps,
pain, paresthesias, carpopedal spasm, muscle
twitching or spasm ( trismus ..) , tetany.
Chvostek signtapping of facial nerve (tap the
Cheek) contraction of facial muscles.
Trousseau signocclusion of brachial artery
with BP cuff (cuff the Triceps) carpal spasm.
HYPOPARATHYROIDISM
Findings: low PTH, hypocalcemia,
hyperphosphatemia.

Treatment : Ca+2 and Vit. D


pseudoHYPOPARATHYROIDISM
(Albright hereditary osteodystrophy)
unresponsiveness of kidney to PTH
hypocalcemia despite highPTH levels.
Characterized by shortened 4th/5th digits, short
stature.
Autosomal dominant.
Due to defective Gs protein -subunit causing
end-organ resistance to PTH.
Defect must be inherited from mother due to
imprinting.
pseudopseudoHYPOPARATHYROIDISM
physical exam features of Albright hereditary
osteodystrophy but without end-organ PTH
resistance.
Occurs when defective Gs protein -subunit is
inherited from father.
Familial hypocalciuric
hypercalcemia
Defective Ca2+-sensing receptor (CaSR) in
multiple tissues (eg, parathyroids, kidneys).
Higher than normal Ca2+ levels required to
suppress PTH.
Excessive renal Ca2+ reuptake
mild hypercalcemia and hypocalciuria with
normal to PTH levels.
v.s 1ry hyperPTH.
hyperPTH
3 types :
1ry.
2ry.
3ry.
1ry hyperPTH
Usually due to parathyroid adenoma or
hyperplasia. Cancer in very very very rare
cases .
Hypercalcemia, hypercalciuria (renal stones),
hypophosphatemia, high PTH, highALP, high
cAMP in urine.
1ry hyperPTH
Most often asymptomatic.
May present with loss of appetite, weakness
and constipation (groans), abdominal/flank
pain (kidney stones, acute pancreatitis),
depression (psychiatric overtones).
ECG : short QT interval.
1ry hyperPTH
Bone changes :
Osteitis fibrosa cysticacystic bone spaces
filled with brown fibrous tissue (brown
tumor consisting of osteoclasts and
deposited hemosiderin from hemorrhages;
causes bone pain).
1ry hyperPTH
1ry hyperPTH
1ry hyperPTH
SECONDARY
HYPERPARATHYROIDISM
2 hyperplasia due to decreasedCa2+
absorption and/or high PO4,
most often in chronic renal disease (causes
hypovitaminosis D Ca2+ absorption).
Hypocalcemia,hyperphosphatemia in chronic
renal failure (vs hypophosphatemia with most
other causes ( vit.D def)).
High ALP, HighPTH.
SECONDARY
HYPERPARATHYROIDISM
Renal osteodystrophyrenal disease 2
and 3 hyperparathyroidism bone lesions.
TERTIARY
HYPERPARATHYROIDISM
Refractory (autonomous) hyperparathyroidism
resulting from chronic renal disease.
very high PTH, highCa2+.
Thyroid hormones
(T3/T4)
Iodine-containing hormones that control the
bodys metabolic rate.
Source:
Follicles of thyroid.
Most T3 formed in target tissues.
Thyroid hormones
(T3/T4)
Function :
Bone growth (synergism with GH)
CNS maturation
Thyroid hormones
(T3/T4)
increase 1 receptors in heart = increasesCO,
HR, SV, contractility.

basal metabolic rate by increasing Na+/K+-


ATPase activity increasesO2 consumption,
RR, body temperature.
Thyroid hormones
(T3/T4)
increasesglycogenolysis, gluconeogenesis,
lipolysis
Thyroid hormones
(T3/T4)
Regulation :
TRH (hypothalamus) stimulates TSH
(pituitary), which stimulates follicular cells.
Negative feedback by free T3, T4 to anterior
pituitary sensitivity to TRH.
Thyroid hormones
(T3/T4)
Thyroid hormones
(T3/T4)
Thyroxine-binding globulin (TBG) binds most
T3/T4 in blood; only free hormone is active.
TBG decreases in hepatic failure, steroids;
TBG increases in pregnancy or OCP use
(estrogen stimulatesTBG production).
Mechanism ?
Thyroid hormones
(T3/T4)
Thyroid hormones
(T3/T4)
T3 binds nuclear receptor with greater affinity
than T4.
T4 is major thyroid product; converted to T3 in
peripheral tissue by 5-deiodinase.
Drugs that inhibit T4T3 conversion :
(PTU, Steroids, BB , amiodarone)
Thyroid hormones
(T3/T4)
Thyroid peroxidase is the enzyme responsible
for oxidation and organification of iodide as
well as coupling of monoiodotyrosine (MIT) and
di-iodotyrosine (DIT).
DIT + DIT = T4.
DIT + MIT = T3.
Thyroid hormones
(T3/T4)
Propylthiouracil inhibits both thyroid
peroxidase and 5-deiodinase.
Methimazole inhibits thyroid peroxidase only.
Thyroid hormones
(T3/T4)
Wolff-Chaikoff effectexcess iodine
temporarily inhibits thyroid peroxidase
decreases iodine organification decreased
T3/T4 production.
THYROID-RELATED DISORDERS
Hyperthyroidism.
Hypothyroidism.
goiter
myxedema
THYROID-RELATED DISORDERS
Both HYPER and HYPOTHYROID couse HTN

The most sensitive hormone in thyroid is TSH


?
THYROID-RELATED DISORDERS
High T3,T4 + low TSH ?
High T3,T4 + high TSH ?
Low T3,T4 + high TSH ?
Low T3,T4 + low TSH ?
Normal T3,T4 + low TSH ?
Low T3, T4 + normal TSH ?
Goiter
Enlargement of thyroid gland.
Mostly euthyroid.
Goiter
hypothyroidism
Hashimoto thyroiditis
Congenital hypothyroidism (cretinism)
Subacute granulomatous thyroiditis (de
Quervain)
Riedel thyroiditis
others
Hashimoto thyroiditis
autoimmune disorder ( T4HR) with antithyroid
peroxidase (antimicrosomal) and
antithyroglobulin antibodies (markers not
mediaters).
Associated with HLA-DR5.
Most common cause of hypothyroidism in
iodine-sufficient regions
Hashimoto thyroiditis
risk of non-Hodgkin lymphoma (typically of B-
cell origin).
Hashimoto thyroiditis
May be hyperthyroid early in course due to
thyrotoxicosis during follicular rupture.
Findings: moderately enlarged, nontender
thyroid.
Hashimoto thyroiditis
Histologic findings: Hrthle cells, lymphoid
aggregates with germinal centers .
Hashimoto thyroiditis
TTT : thyroid replacement therapy
Congenital hypothyroidism
(cretinism)
Severe fetal hypothyroidism.
Causes :
thyroid dysgenesis(most common cause )
maternal hypothyroidism
thyroid agenesis
iodine deficiency
dyshormonogenetic goiter.
Congenital hypothyroidism
(cretinism)
Findings: Pot-bellied, Pale, Puffy-faced child
with Protruding umbilicus, Protuberant
tongue, short stature and Poor brain
development.
Subacute granulomatous thyroiditis
(de Quervain)
Self-limited disease often following a flu-like
illness (eg, viral infection).
Occurs in young females.
May be hyperthyroid early in course, followed
by hypothyroidism.
Histology: granulomatous inflammation.
Findings: ESR, jaw pain, very tender thyroid.
TTT: NSAID
Riedel thyroiditis
Thyroid replaced by fibrous tissue with
inflammatory infiltrate.
Fibrosis may extend to local structures (eg,
trachea, esophagus), mimicking anaplastic
carcinoma.
13 are hypothyroid.
Findings: fixed, hard (rock-like), painless
goiter.
Riedel thyroiditis
Considered a manifestation of IgG4-related
systemic disease (eg, autoimmune
pancreatitis, retroperitoneal fibrosis,
noninfectious aortitis).
others
Iodine deficiency , goitrogens (eg,
amiodarone, lithium), Wolff-Chaikoff effect
(thyroid gland downregulation in response to
iodide).
Hyperthyroidism
Graves disease.
Toxic multinodular goiter \ Toxic adenoma.
Thyroid storm.
Jod-Basedow phenomenon.
Graves disease.
Most common cause of hyperthyroidism.
Thyroid-stimulating immunoglobulin (IgG;
type II hypersensitivity) stimulates TSH
receptors on thyroid (hyperthyroidism, diffuse
goiter) and dermal fibroblasts (pretibial
myxedema).
Often presents during stress (eg, pregnancy).
pretibial myxedema
Graves disease.
Infiltration of retroorbital space by activated
T-cells increasedcytokines (eg, TNF-, IFN-
) increased fibroblast secretion of
hydrophilic GAGs osmotic muscle swelling,
muscle inflammation, and adipocyte count
exophthalmos .
exophthalmos
Graves disease.
Bx: Tall, crowded follicular epithelial cells;
scalloped colloid
Graves disease.
Dx:
Hyperthyriodism.
Thyroid-stimulating immunoglobulin +ve
Increase uptake

TTT: antithyroid medications , surgery ,


radioactive iodine.
Toxic multinodular goiter
Focal patches of hyperfunctioning follicular
cells .
working independently of TSH (due to TSH
receptor mutations in 60% of cases).
release of T3 and T4.
Hot nodules are rarely malignant.
Thyroid storm
Uncommon but serious complication that
occurs when hyperthyroidism is incompletely
treated/untreated and then significantly
worsens in the setting of acute stress such as
infection, trauma,surgery.
Thyroid storm
Presents with agitation, delirium, fever,
diarrhea, coma, and tachyarrhythmia (cause
of death).
May see high LFTs
Thyroid storm
TTT:
-blockers (eg, Propranolol)
Propylthiouracil
corticosteroids (eg, Prednisolone)
Potassium iodide (Lugol iodine).
Jod-Basedow phenomenon
Thyrotoxicosis if a patient with iodine
deficiency and partially autonomous thyroid
tissue (eg, autonomous nodule) is made
iodine replete.
Opposite of Wolff-Chaikoff effect.
Thyroid Nodule
Thyroid Adenoma
Benign solitary growth of the thyroid.
Most are nonfunctional (cold), can rarely
cause hyperthyroidism via autonomous
thyroid hormone production (hot or
toxic).
Most common histology is follicular
absence of capsular or vascular invasion
(unlike follicular carcinoma).
Thyroid cancer
Papillary carcinoma.
Follicular carcinoma.
Medullary carcinoma.
Undifferentiated/anaplastic carcinoma.
Lymphoma
Papillary carcinoma.
Most common, excellent prognosis ,
irradiation
Empty-appearing nuclei with central clearing
(Orphan Annie eyes)
psammoma bodies
nuclear grooves.
risk with RET and BRAF mutations,
Papillary carcinoma.
Follicular carcinoma.
Good prognosis.
invades thyroid capsule and vasculature
(unlike follicular adenoma)
Uniform follicles;
hematogenous spread is common.
Associated with RAS mutation.
Follicular Carcinoma v.s Adenoma
FNA can not distinguish them so cut biopsy.
Medullary carcinoma
From parafollicular C cells; produces
calcitonin (mostly inactive) BUT may lead to
sheets of cells in an amyloid stroma (stains
with Congo red ).
Associated with MEN 2A and 2B (RET
mutations).
Medullary carcinoma
Undifferentiated/anaplastic
carcinoma.
Older patients; invades local structures, very
poor prognosis.
Lymphoma
Associated with Hashimoto thyroiditis.
Thyroid Cancers TTT
Treated with thyroidectomy + Radioactive
Iodie.
Thyroid Cancers TTT
Complications of surgery include:
hoarseness (due to recurrent laryngeal nerve
damage).
Loss of High pitched sound (due to SLN palsy)
and transection of recurrent and superior
laryngeal nerves (during ligation of inferior
thyroid artery and superior laryngeal artery,
respectively).
hypocalcaemia (due to removal of parathyroid
glands).
Antidiuretic hormone (ADH)
Synthesized in hypothalamus (supraoptic nuclei),
stored and secreted by posterior pituitary.
Regulates serum osmolarity (V2-receptors)and
blood pressure (V1-receptors).
Primary function is serum osmolarity regulation
(ADH decreasesserum osmolarity, increase urine
osmolarity) via regulation of aquaporin channel
insertion in principal cells of renal collecting duct.
Antidiuretic hormone (ADH)
Regulation : Osmoreceptors in hypothalamus;
hypovolemia.
Antidiuretic hormone (ADH)-realted
disorders
DI
SIADH
Diabetes Insipides
Characterized by intense thirst and polyuria
with inability to concentrate urine due to lack
of ADH activity :
No ADH (central) .
or failure of response to circulating ADH
(nephrogenic).
Diabetes Insipides
Syndrome of inappropriate
antidiuretic hormone secretion
Characterized by:
Excessive free water retention
Euvolemic hyponatremia with continued
urinary Na+ excretion
Urine osmolality > serum osmolality
Syndrome of inappropriate
antidiuretic hormone secretion
Body responds to water retention with
Decrease aldosterone and increaseANP and
BNP urinary Na+ secretion normalization
of extracellular fluid volume euvolemic
hyponatremia.
Syndrome of inappropriate
antidiuretic hormone secretion
Very low serum Na+ levels can lead to cerebral
edema seizures
Syndrome of inappropriate
antidiuretic hormone secretion
Causes include:
Ectopic ADH (eg, small cell lung cancer)
CNS disorders/head trauma
Pulmonary disease (COPD , Pseumonia)
Drugs (eg, cyclophosphamide , anti-
depressants)
Syndrome of inappropriate
antidiuretic hormone secretion
Treatment: fluid restriction, salt tablets, IV
hypertonic saline, diuretics, conivaptan,
tolvaptan, demeclocycline.
Syndrome of inappropriate
antidiuretic hormone secretion
Correct slowly to prevent osmotic
demyelination syndrome (formerly known as
central pontine myelinolysis).
Insulin
Preproinsulin (synthesized in RER) cleavage
of presignal proinsulin (stored in
secretory granules) cleavage of proinsulin
exocytosis of insulin and C-peptide equally.
Insulin
Insulin and C-peptide are in insulinoma and
sulfonylurea use .
exogenous insulin lacks C-peptide.
Insulin
Insulin
Insulin
Unlike glucose, insulin does not cross
placenta.
Gestational DM ??
Insulin
Insulin-dependent glucose transporters:
GLUT-4: adipose tissue, striated muscle (exercise
can also increase GLUT-4 expression)
Insulin-independant transporters:
GLUT-1: RBCs, brain, cornea, placenta.
GLUT-2 (bidirectional): islet cells, liver, kidney (
SGLT-2), small intestine ( basolateral)
GLUT-3: brain, placenta.
GLUT-5 (fructose): spermatocytes, GI tract
Insulin
Brain utilizes glucose for metabolism normally
and ketone bodies during starvation.
RBCs always utilize glucose because they lack
mitochondria for aerobic metabolism.
Insulin
Glucagon
Made by cells of pancreas.

Catabolic effects of glucagon:


increases Glycogenolysis, gluconeogenesis.
increases Lipolysis and ketone production.
Glucagon
Secreted in response to hypoglycemia.
Inhibited by insulin, hyperglycemia, and
somatostatin.
Insulin
Glucose is the major regulator of insulin
release.
insulin response with oral vs IV glucose
because of incretins such as glucagon-like
peptide 1 (GLP-1), which are released after
meals and cell sensitivity to glucose.
Insulin
Stimulation of B2 sympathetic receptors
increases insulin .
Stimulation of a2 sympathetic receptors
decreases insulin .
If Both ??
Diabetes Mellitus
Abnormal Metabolism of Carbohydrates ,
Proteins and Lipids.
Diabetes Mellitus
Diabetes Mellitus
Polydipsia, polyuria, polyphagia, weight loss.

Acute complications : DKA (type 1),


hyperosmolar coma (type 2).
Diabetes Mellitus
Insulin def. or Insulin resistence.
can be caused by unopposed secretion of GH
and epinephrine.
Also seen in patients on glucocorticoid
therapy (steroid diabetes).
Diabetes Mellitus
Diabetes Mellitus
Chronic Complications:
Nonenzymatic glycation:
Small vessel disease (diffuse thickening of basement
membrane) retinopathy (hemorrhage,exudates,
microaneurysms, vessel proliferation), glaucoma,
neuropathy, nephropathy (nodular glomerulosclerosis,
aka Kimmelstiel-Wilson nodules progressive
proteinuria [initially microalbuminuria; ACE inhibitors
are renoprotective] and arteriolosclerosis
hypertension; both lead to chronic renal failure).
Diabetes Mellitus
Large vessel atherosclerosis, CAD, peripheral
vascular occlusive disease, gangrene limb
loss, cerebrovascular disease. MI most
common cause of death
Diabetes Mellitus
Osmotic damage (sorbitol accumulation in
organs with aldose reductase and or absent
sorbitol dehydrogenase):
Neuropathy (motor, sensory [glove and
stocking distribution], and autonomic
degeneration)
Cataracts
Diabetes Mellitus
Diabetes Mellitus
Acute Complications:
Diabetic ketoacidosis
Hyperosmolar hyperglycemic non-ketotic
syndrome.
Diabetic ketoacidosis
One of the most feared complications of
diabetes.
ABSOLUTE INSULIN DEF. : Usually due to insulin
noncompliance , increaseinsulin requirements
from stress (eg, infection) or first presentation.
Excess fat breakdown and ketogenesis from free
fatty acids, which are then made into ketone
bodies (-hydroxybutyrate > acetoacetate).
Usually occurs in type 1 diabetes, as endogenous
insulin in type 2 diabetes usually prevents
lipolysis.
Diabetic ketoacidosis
Presentation :
Delirium/psychosis.
Kussmaul respirations (rapid/deep breathing).
Abdominal pain/nausea/vomiting.
Dehydration.
Fruity breath odor (due to exhaled acetone).
Diabetic ketoacidosis
Hyperglycemia 300-400
high H+ low PH , acidosis (anion gap
metabolic acidosis).
lowHCO3
blood ketone levels,
leukocytosis.
Hyperkalemia.
Diabetic ketoacidosis
Hyperkalemia :
due to transcellular shift from
low insulin ,
acidosis (therefore total body K+ is depleted)
and hyperosmolarity.
Diabetic ketoacidosis
Complications:
Life-threatening mucormycosis (usually caused
by Rhizopus infection).
cerebral edema.
cardiac arrhythmias
heart failure.
Mucormycosis
Headache, facial pain, black necrotic eschar on
face.
Diabetic ketoacidosis
TTT:
IV fluids.
IV insulin ( Regular)
K+ (to replete intracellular stores).
glucose if necessary to prevent hypoglycemia.
Hyperosmolar hyperglycemic non-
ketotic syndrome.
State of profound hyperglycemia-induced
dehydration and high serum osmolarity.
classically seen in elderly type 2 diabetics
with limited ability to drink.
Hyperglycemia excessive osmotic diuresis
dehydration eventual onset of HHNS.
Symptoms: thirst, polyuria, lethargy, focal
neurological deficits (eg, seizures), can
progress to coma and death if left untreated.
Hyperosmolar hyperglycemic non-
ketotic syndrome.
Labs:
hyperglycemia (often > 600 mg/dL).
serum osmolarity (> 320 mOsm/kg).
no acidosis (pH >7.3, ketone production
inhibited by presence of insulin).
Hyperosmolar hyperglycemic non-
ketotic syndrome.
Treatment: aggressive IV fluids, insulin
therapy.
Insulinoma
Tumor of pancreatic cells overproduction of insulin
hypoglycemia.
May see Whipple triad:
low blood glucose.
symptoms of hypoglycemia (eg, lethargy, syncope,
diplopia)
and resolution of symptoms after normalization of glucose
levels.
Symptomatic patients have low blood glucose and highC-
peptide levels (vs exogenous insulin use).
10% of cases associated with MEN 1 syndrome.
Treatment: surgical resection
Glucagonoma
Tumor of pancreatic cells overproduction
of glucagon.
Presents with dermatitis (necrolytic
migratory erythema), diabetes
(hyperglycemia), DVT, declining weight,
depression.
Treatment: octreotide, surgery.
(necrolytic migratory erythema)
Hypoglycemia
DDx:
Insulinoma .
Sulfonylurea
Exogenous insulin
How to differentiate ?
Hypoglycemia
Management :
Conscious : oral glucose .
Confused\comatosed : glucagon , IV glucose.
Adrenals
Cortisol
Blood pressure:
Upregulates 1-receptors on arterioles increases
sensitivity to norepinephrine and Epinephrine .
At high concentrations, can bind to mineralocorticoid
(aldosterone) receptors.
increases Insulin resistance (diabetogenic)
increases Gluconeogenesis
Increases Lipolysis redistribution of fat.
Increases proteolysis
decreasesBone formation (decreased osteoblast
activity)
Cortisol
decreasesFibroblast activity (causes striae)
Microhemprrhages.
Cortisol
Inflammatory and Immune responses:
Inhibits production of leukotrienes and
prostaglandins.
Inhibits WBC adhesion neutrophilia
Blocks histamine release from mast cells
Reduces eosinophils
Blocks IL-2 production no T-cell
proliferation.
Cortisol
Exogenous corticosteroids can cause
reactivation of TB and candidiasis (blocks IL-2
production).
Cortisol
Fetal lungs maturity.
Cortisol
Regulation :
CRH (hypothalamus) stimulates ACTH release
(pituitary) cortisol production in adrenal zona
fasciculata.
Excess cortisol inhibitsCRH,ACTH, and cortisol
secretion.
Cortisol
Chronic stress induces prolonged secretion.
Fluctuation in Cortisol secretion during the
day.
Cortisol
High level of cortisol inhibits GHRH.
ALdosterone
Acts mainly on late distal convoluted tubules
and collecting ducts :
Na+ reabsorption
K+ and H+ loss .
Cushing syndrome
cortisol due to a variety of causes =
hypercortisolism.
Presentation : Hypertension, weight gain,
moon facies , abdominal striae , and truncal
obesity, buffalo hump,skin changes (thinning,
striae), osteoporosis, hyperglycemia (insulin
resistance), amenorrhea,immunosuppression,
skeletal muscle atrophy.
Cushing syndrome
Cushing syndrome
Causes :
Exogenous corticosteroids (Most common
cause)
Primary adrenal adenoma, hyperplasia, or
carcinoma.
ACTH-secreting pituitary adenoma (Cushing
disease); paraneoplastic ACTH secretion (eg,
small cell lung cancer, bronchial carcinoids)
Cushing syndrome
Dx :
free cortisol on 24-hr urinalysis.
midnight salivary cortisol.
and no suppression with overnight low-dose
dexamethasone test.
Cushing syndrome
Confirm :
High-dose Dexamethasone suppression test.
Cushing syndrome
Localize :
ACTH imaging
Cushing syndrome
Hyperaldosteronism
Presentation : HTN , HypoK+ and metabolic
acidosis.
Why no HyperNA+ ??
1ry v.s 2ry.
Adrenal insufficiency
Inability of adrenal glands to generate enough
glucocorticoids +/ mineralocorticoids for the
bodys needs.
Adrenal insufficiency
Symptoms include weakness, fatigue,
orthostatic hypotension, hypotension, muscle
aches, weight loss, GI disturbances, sugar
and/or salt cravings ( hypoglycemia \
hyponatremia).
Adrenal insufficiency
Diagnosis involves measurement of serum
electrolytes, morning/random serum cortisol
and ACTH (low cortisol, high ACTH in 1 adrenal
insufficiency; low cortisol, low ACTH in 2/3
adrenal insufficiency due to pituitary/
hypothalamic disease), and response to ACTH
stimulation test.
Adrenal insufficiency
Alternatively, can use metyrapone stimulation
test:
metyrapone blocks last step of cortisol synthesis
(11-deoxycortisol cortisol).
Normal response is decrease in cortisol and
compensatory increaseACTH and 11-
deoxycortisol.
In 1 adrenal insufficiency, ACTH is high but 11-
deoxycortisol remains lowafter test.
In 2/3 adrenal insufficiency, both ACTH and 11-
deoxycortisol remain lowafter test.
Primary adrenal
insufficiency
Deficiency of aldosterone and cortisol
production due to loss of gland function.
hypotension (hyponatremic volume
contraction), hyperkalemia, metabolic
acidosis, skin and mucosal hyperpigmentation
.
Primary adrenal
insufficiency
Primary adrenal
insufficiency
Acute
sudden onset (eg, due to massive
hemorrhage)
May present with shock in acute adrenal crisis
.
causes of hemorrhage ?
Primary adrenal
insufficiency
Waterhouse-Friderichsen syndromeacute 1
adrenal insufficiency due to adrenal
hemorrhage associated with septicemia
(usually Neisseria meningitidis), DIC, endotoxic
shock.
Primary adrenal
insufficiency
Chronicaka Addison disease.
Due to adrenal atrophy or destruction by
disease (autoimmune destruction most
common in the Western world; TB most
common in the developing world).
Secondary adrenal
insufficiency
Seen with lowpituitary ACTH production.
No skin/mucosal hyperpigmentation.
no hyperkalemia (aldosterone synthesis
preserved).
Tertiary adrenal
insufficiency
Seen in patients with chronic exogenous
steroid use, precipitated by abrupt
withdrawal.
Aldosterone synthesis unaffected.
Adrenal insufficiency
Treatment: glucocorticoid/ mineralocorticoid
replacement.
Congenital Adrenal Hyperplasia
Congenital Adrenal Hyperplasia
Congenital Adrenal Hyperplasia
aAll congenital adrenal enzyme deficiencies
are characterized by an enlargement of both
adrenal glands due to ACTH stimulation (in
response to cortisol).
Ttt : Corticosteroids.
Neuroendocrine
tumors
Group of neoplasms originating from Kulchitsky
and enterochromaffin-like cells.
Occur in various organs (eg, thyroid: medullary
carcinoma; lungs: small cell carcinoma; pancreas:
islet cell tumor; adrenals: pheochromocytoma).
Cells contain amine precursor uptake
decarboxylase (APUD) and secrete different
hormones (eg, 5-HIAA, neuron-specific enolase
[NSE], chromogranin A).
Neuroblastoma
Most common tumor of the adrenal medulla
in children, usually < 4 years old.
Originates from neural crest cells.
Occurs anywhere along the sympathetic chain
Neuroblastoma
Most common presentation is abdominal
distension and a firm, irregular mass that can
cross the midline (vs Wilms tumor, which is
smooth and unilateral).
Less likely to develop hypertension than with
pheochromocytoma.
Can also present with opsoclonus-myoclonus
syndrome (dancing eyes-dancing feet).
Neuroblastoma
highHVA and VMA (catecholamine
metabolites) in urine.
Homer-Wright rosettes characteristic of
neuroblastoma and medulloblastoma.
Bombesin and NSE .
Associated with overexpression of N-myc
oncogene.
Classified as an APUD tumor.
Neuroblastoma
Pheochromocytoma
Most common tumor of the adrenal medulla
in adults.
Derived from chromaffin cells (arise from
neural crest).
Up to 25% of cases associated with germline
mutations (eg, NF-1, VHL, RET [MEN 2A, 2B]).
Pheochromocytoma
Rule of 10s:
10% malignant
10% bilateral
10% extra-adrenal
10% calcify
10% kids
Pheochromocytoma
Most tumors secrete epinephrine,
norepinephrine, and dopamine, which can
cause episodic hypertension.
Symptoms occur in spellsrelapse and
remit.
Pheochromocytoma
D
x: catecholamines and metanephrines in
urine and plasma.
Pheochromocytoma
Irreversible -antagonists (eg,
phenoxybenzamine) followed by -
blockersprior to tumor resection.
-blockade must be achieved before giving -
blockers to avoid a hypertensive crisis.
Hypopituitarism
Undersecretion of pituitary hormones due to:
Nonsecreting pituitary adenoma,
craniopharyngioma
Sheehan syndromeischemic infarct of
pituitary following postpartum bleeding;
pregnancyinduced pituitary growth
susceptibility to hypoperfusion. Usually
presents with failure to lactate, absent
menstruation, cold intolerance.
Hypopituitarism
E mpty sella syndromeatrophy or compression of
pituitary (which lies in the sella turcica), often
idiopathic, common in obese women.
Pituitary apoplexysudden hemorrhage of pituitary
gland, often in the presence of an existing pituitary
adenoma. Usually presents with sudden onset severe
headache, visual impairment (eg, bitemporal
hemianopia, diplopia due to CN III palsy), and features
of hypopituitarism.
Brain injury
Radiation
Hypopituitarism
Treatment: hormone replacement therapy
(corticosteroids, thyroxine, sex steroids,
human growth hormone).
Nelson syndrome
Enlargement of existing ACTH-secreting
pituitary adenoma after bilateral
adrenalectomy for refractory Cushing disease
(due to removal of cortisol feedback
mechanism).
Presents with hyperpigmentation, headaches
and bitemporal hemianopia.
Treatment: pituitary irradiation or surgical
resection.
Multiple endocrine
neoplasias (MEN)
MEN 1
Pituitary tumors (prolactin or GH)
Pancreatic endocrine tumorsZollinger-
Ellison syndrome, insulinomas, VIPomas,
glucagonomas (rare)
Parathyroid adenomas
Associated with mutation of MEN1 (menin, a
tumor suppressor, chromosome 11)
Multiple endocrine
neoplasias (MEN)
MEN 2A
Parathyroid hyperplasia
Medullary thyroid carcinomaneoplasm of
parafollicular or C cells; secretes calcitonin;
prophylactic thyroidectomy required
Pheochromocytoma (secretes catecholamines)
Associated with mutation in RET (codes for
receptor tyrosine kinase) in cells of neural crest
origin
Multiple endocrine
neoplasias (MEN)
MEN 2B :
Medullary thyroid carcinoma
Pheochromocytoma
Mucosal neuromas (oral/intestinal
ganglioneuromatosis)
Associated with marfanoid habitus
mutation in RET gene
Mucosal neuromas
Marfanoid habitus