Basic Endocrinology

Omar Ali MD
 A bit of history
 Early 19th century: Secretions from glands
are carried by ducts and act at specific
sites.
 Late 19th century: several investigators
discovered that some glands seem to
secrete chemicals directly into the blood
(“ductless glands”) and these act far from
where they are secreted.
Arnold A Berthold
(1803-1861)
 Inone of the first endocrine
experiments ever recorded,
Professor Arnold A. Berthold
of Gottingen did a series of
tests on roosters in 1849
while he was curator of the
local zoo.
 Ablation and replacement
•Berthold found that a rooster's comb is an
androgen-dependent structure. Following
castration, the comb atrophies, aggressive male
behavior disappears, and interest in the hens is
lost.
•Importantly, Berthold also found that these
castration-induced changes could be reversed by
administration of a crude testicular extract (or
prevented by transplantation of the testes).
Claude Bernard
(1813-1878)

Claude Bernard stated that the

endocrine system regulates the
internal milieu of an animal. The
“internal secretions” were
liberated by one part of the body,
traveled via the bloodstream to
distant targets cells. Circa 1854
 Endocrine system maintains
homeostasis
The concept that hormones acting on distant target
cells to maintain the stability of the internal
milieu was a major advance in physiological
understanding.
The secretion of the hormone was evoked by a
change in the milieu and the resulting action on
the target cell restored the milieu to normal.
The desired return to the status quo results in
the maintenance of homeostasis
 Two control systems

Nervous system.
Endocrine system
Nervous system

•The nervous system exerts

point-to-point control through
nerves, similar to sending
messages by conventional
telephone. Nervous control is
electrical in nature and fast.
 Hormones travel via the
bloodstream to target cells
•The endocrine system broadcasts its
hormonal messages to essentially all
cells by secretion into blood and
extracellular fluid. Like a radio
broadcast, it requires a receiver to get
the message - in the case of endocrine
messages, cells must bear a receptor
for the hormone being broadcast in
order to respond.
 A cell is a target because it has a specific
receptor for the hormone

Most hormones circulate in blood, coming into contact with essentially

all cells. However, a given hormone usually affects only a limited
number of cells, which are called target cells. A target cell
responds to a hormone because it bears receptors for the hormone.
 Response vs. distance traveled
Endocrine action: the hormone is distributed in blood and binds to
distant target cells.
Paracrine action: the hormone acts locally by diffusing from its
source to target cells in the neighborhood.
Autocrine action: the hormone acts on the same cell that produced
it.
 Control of Endocrine Activity

•The physiologic effects of hormones depend

largely on their concentration in blood and
extracellular fluid.
•Almost inevitably, disease results when hormone
concentrations are either too high or too low, and
precise control over circulating concentrations of
hormones is therefore crucial.
 Feedback Control of Hormone
Production
Feedback loops are used
extensively to regulate
secretion of hormones in the
hypothalamic-pituitary axis.
An important example of a
negative feedback loop is seen
in control of thyroid hormone
secretion
 Feedback control
 Negative feedback is most common: for
example, LH from pituitary stimulates the testis
to produce testosterone which in turn feeds back
and inhibits LH secretion
The Endocrine System

Figure 18.1
Importance of the hypothalamus in homeostasis

Regulates body temperature, sense of hunger,

water balance

Also controls the pituitary gland

Pituitary helps regulate other glands

Negative feedback keeps things stable

The Hypophyseal Portal System

Figure 18.7
 The posterior lobe of the
pituitary gland
 Contains axons of hypothalamic nerves.
These release hormones that are
synthesized in the hypothalamus and
transported down to the post. pituitary
 neurons of the supraoptic nucleus
manufacture antidiuretic hormone (ADH)
Decreases the amount of water lost at the
kidneys. Makes the urine more
concentrated.
At higher doses: Elevates blood pressure
 The posterior lobe of the
pituitary gland
(neurohypophysis)
 Neuronsof the paraventricular nucleus
manufacture oxytocin
 Stimulates contractile cells in mammary
glands
 Stimulates smooth muscle cells in uterus
 Thyroid stimulating hormone (TSH)
 Thyrotropin releasing hormone promotes the
release of TSH
 TSH stimulates synthesis and release of thyroid
hormones
 Adrenocorticotropic hormone (ACTH)
 Corticotrophin releasing hormone causes the
secretion of ACTH
 ACTH stimulates the release of glucocorticoids
from the adrenal gland
• Gonadotropin releasing hormone (GNRH)
promotes the secretion of FSH and LH
 Follicle stimulating hormone (FSH)
 Stimulates follicle development and estrogen
secretion in females and sperm production in males
 Leutinizing hormone (LH)
 Causes ovulation and progestin production in
females and Testosterone production in males
 Prolactin (PH)
 Stimulates the development of mammary glands
and milk production. Not essential?
 Growth hormone (GH or somatotropin)
 Stimulates cell growth and replication through
release of somatomedins or IGFs by the liver
 Also stimulates the production of IGF binding
protein 3 and ALS.
 Growth
 Fat and short is the most worrying
combination
 Not an emergency, so refer.
 Accurate growth charts and parent heights
are very important.
 Rule out obvious causes of
malnutrition/chronic illness
 Normal Variant Short
Stature
+2 SD =97th percentile
mean
-2 SD =3rd percentile

150 -4 SD
Height (cm)

GHD
100 Constitutional Delay

Familial SS
Males 3-18 years
4 6 8 10 12 14 16 18
Age (years)
Diagnostic Workup
• Complete blood cell count (CBC)
• Erythrocyte sedimentation rate (ESR)
• Electrolytes
• Chemistry panel
• Urinalysis
• T4/TSH
• IGF-1 (somatomedin C) and IGFBP-3
• Dietary evaluation

27
 BONE AGE
 Mostcommon
standards for bone
ages are those of
Gruelich and Pyle

 Left hand and wrist

film
 Rules of Growth
Evaluation
6. A rock will grow if given enough growth hormone.

7. Growth hormone deficiency is the toughest disease to

diagnose but the easiest to treat.

8. If your height and weight curves meet, you are in

trouble.

9. If your weight is on the height curve, you are obese.

10. If your height is in the weight curve, you are short.

 Thyroid hormones

Thyroxine (T4) and T3.

T4 is converted to T3 peripherally, which is
the active form
Exert a calorigenic effect
Increase metabolic rate
So: increased heart rate, body temperature,
energy use, appetite, growth etc etc.
 Hypothyroidism
 Thyroid hormone deficiency causing a
decrease in the basal metabolic rate
 Person is “slowed down”
 Causes of Primary Hypothyroidism:
 Congenital thyroid aplasia
 Radioactive iodine ablation
 Hashimoto’s thyroiditis - autoimmune destruction
 Non-compliance with levothyroxine
 Hypothyroidism
 Confusion, drowsiness, coma
 Cold intolerance
 Hypotension, Bradycardia
 Muscle weakness
 Decreased respirations
 Weight gain, Constipation
 Non-pitting peripheral edema
 Depression
 Facial edema, loss of hair
 Dry, coarse skin
 Earliest
sign is SLOWING
GROWTH
Appearance of
Myxedema
 Hyperthyroidism
 Excessive levels of thyroid levels cause
hypermetabolic state
 Person is “sped up”.
 Causes of Hyperthyroidism
 Grave’s Disease
 Overmedication with levothyroxine (Synthroid®)
 Adenoma
 Hyperthyroidism
 Nervousness, irritable, tremors,
paranoid
 Warm, flushed skin
 Heat intolerance
 Tachycardia - High output CHF
 Hypertension
 Tachypnea
 Diarrhea
 Weight loss with increased
appetite
 Exophthalmos
 Goiter
Exophthalmos
 C-Cells of the thyroid
gland

C cells produce calcitonin

 Helps regulate calcium concentration in body
fluids. Decreases calcium levels.
 Not as important as PTH
 Thyroid disorders
 Screen for hypothyroidism by measuring Free
thyroxine by dialysis and TSH.
 If hyperthyroidism is suspected, also test for
free T3
 Anti-thyroglobulin and anti-thyroperoxidase
antibodies
 Thyroid stimulating antibody for Grave’s
disease.
The Parathyroid Glands

Figure 18.14
 PTH
 Secreted in response to low serum
calcium
 Reduces urinary calcium excretion and
increases phosphate excretion
 Increased calcium mobilization from bone
 Stimulates activation of Vitamin D, which
increases calcium and phosphorous
absorption in the gut.
 Net effect is to increase serum Ca.
 Adrenal cortex
 Manufactures steroid hormones
(corticosteroids)
 Cortex divided into three layers
 Zona glomerulosa (produces
mineralocorticoids)…salty
 Zona fasciculate (produces
glucocorticoids)..sweet
 Zona reticularis (produces androgens)..sexy
 Adrenal disorders
 Primary: disorder in the adrenal gland
itself (adenoma->XS production, infiltrative
disease or infarction ->deficiency)
 Secondary: disorder in the hypothalamus
or pituitary gland causing abnormal ACTH
release (excessive ->hyperadrenalism,
deficient -> hypoadrenalism or adrenal
insufficiency)
 Abnormal Adrenal Function
 Hyperadrenalism
 Hyperaldosteronism (Conn’s syndrome)
 Cushing’s Syndrome & Disease
 Hyperandrogenism (virilization)
 Pheochromocytoma
 Hypoadrenalism (adrenal insufficiency)
 Inadequate activity of the adrenal gland
 Addison’s disease
 Hyperadrenalism
 Cushing’s Syndrome
 Results from increased adrenocortical secretion of
cortisol
 Causes include:
ACTH-secreting tumor of the pituitary
(Cushing’s disease)
excess secretion of cortisol by a neoplasm
within the adrenal cortex
excess secretion of ACTH by a malignant
growth outside the adrenal gland (esp small cell
lung ca) = ectopic ACTH pdtn
excessive or prolonged administration of
steroids
 Hyperadrenalism
 Cushing’s Syndrome
 Characterized by:
 truncal obesity
 moon face
 buffalo hump
 acne, hirsutism
 abdominal striae
 hypertension
 psychiatric disturbances
 osteoporosis
 Amenorrhea
 Growth failure
 Hyperadrenalism
 Adrenogenital syndrome
 “Bearded Lady”
 Group of disorders caused by adrenocortical hyperplasia or
malignant tumors
 Excessive secretion of adrenocortical steroids especially those
with androgenic effects
 Characterized by
 masculinization of women
 premature sexual development of children
Adrenal enzyme pathways
CAH, 46,XX
CAH, simple-virilizing (21-OHase
deficiency)
 Adrenal Crisis
 When to suspect:
 Patient is sicker than expected.
Hypotensive, hypothermic, hypoglycemic
 Critically ill patient
 Neonate with ambigous genitalia
 Neonate with unexplained sudden illness
associated with dehydration and collapse.
 Labs
Criticalsample. One red top and one
green top tube, store on ice/in freezer.
ACTH
Cortisol
17 hydroxy progesterone in the neonate
 Treatment
 Volume expanders (normal saline,
lactated Ringers)
 Glucose
 Emergency Hydrocortisone.
 25 mg IV in neonates
 50 mg in young children
 100 mg in adolescents.
 Then 30 -40 mg per meter square per day
 Adrenal medulla

 Produces epinephrine (~75 - 80%)

 Produces norepinephrine (~25-30%)
 Pheochromocytoma
 Catecholamine secreting tumor of adrenal medulla
 Presentation
 Anxiety
 Pallor, diaphoresis
 Hypertension
 Tachycardia, Palpitations
 Dyspnea
 Hyperglycemia
 The pancreatic islets

 Clusters
of endocrine cells within the
pancreas called Islets of Langerhans or
pancreatic islets
 Alpha cells secrete glucagons
 Beta cells secrete insulin
 Delta cells secrete somatostatin
 F cells secrete pancreatic polypeptide
 Insulin and glucagon
 Insulin lowers blood glucose by increasing
the rate of glucose uptake and utilization
 Glucagon raises blood glucose by
increasing the rates of glycogen
breakdown and glucose manufacture by
the liver
 The gonads
 Interstitial (Leydig) cells of the testes produce testosterone
 Most important sex hormone in males
 In females, oocytes develop in follicles
 Follicle cells produce estrogens
 Afterovulation, the follicle cells form a corpus luteum that releases a
mixture of estrogens and progesterone
 Early Puberty
 More likely to be benign in girls, more
likely to be pathological in boys.
 Isolated thelarche and premature
adrenarche are generally benign.
 Growth chart is very important.
 Refer girls less than 8 and boys less than
9 years of age.
TANNER
STAGE
TANNER
STAGE
 Delayed puberty
 More likely to be pathological in girls than
boys.
 Refer girls if no pubertal changes by 13
and boys if no changes by 14.
 First finding is thelarche in girls and
testicular enlargement in boys.
 No periods by 16 or within 5 years of
thelarche = referral.
 Adipose tissues secrete

 Leptin, a feedback control for appetite

 Resistin, which reduces insulin sensitivity
 Obesity
 Rarely endocrine
 Tall and fat is almost always nutritional.
 Short and fat deserves a workup
 Thyroid
 Cushings
 Genetic disorders, e.g. PWS
ACANTHOSIS NIGRICANS = HYPERINSULINEMIA=T2DM Risk

•Direct action of insulin on keratin layers.

•Can occur anywhere on the body.
•More common in flexor and extensor folds.
•Goes away with treatment of insulin
resistance.
•Severe cases can progress to skin tags,
usually requiring dermatologic treatment.

Katz et al: Dermatology Online Journal, vol 6, 2000 (dermatology.cdlib.org)

 A Practical CHO-Limited Diet
Avoid ALL Simple Sugars
 No regular sodas, sweetened juices.
 Limit unsweetened juices.

 No foods with >5g sugar/serving.

Limit Complex Carbohydrates
 Bread, Potato, Rice, Pasta, Tortilla
 1-3 Servings 3 times a day only
Avoid Fried/Fatty Foods
 These foods may increase cholesterol
levels and cardiovascular risk
Eat More Lean Proteins
 Pork,Beef<15% fat, skinless poultry
 most fish and shellfish

Use Low or Non- Carbohydrate Snacks

Exercise Goal:
 30min sustained, strenuous exercise 3-5
X/wk
 A Practical CHO-Limited Diet:
METFORMIN
 trade name: Glucophage (Bristol Meyers Squibb)
 classified as an “oral anti-hyperglycemic” agent,
NOT an “oral hypoglycemic”
 primary mechanism of action unknown
 actions include: decreased hepatic
gluconeogenesis, decreased intestinal glucose
transport and increased insulin sensitivity
 works best with a CHO-limited diet
 primary side effect: lactic acidosis (~3/100K pt-
years); contraindicated in renal insufficiency
 Monitor: clinical status, LFTs, RFTs
The Endocrine System

Figure 18.1
 History
 Growth charts/growth pattern/weight loss
and gain.
 Chronic illness/concurrent illnesses/past
illness
 Medications
 Previous treatment for cancer
 Head trauma
 Family history
 Thyroid disease
 Diabetes
 Growth pattern
 Hormone issues
 Hormones at home
 Ethnic background
 Physical examination
 Growth parameters
 Dysmorphic features/midline
defects/proportions
 Goiter
 Skin pigmentation
 Birthmarks
 striae
 Genitalia/Tanner stage
 Screening at birth
 Hypothyroidism.
 1/5000 babies
 Usually screen by checking TSH
 California standard >25
 May miss some babies.
 Repeat and treat if really high.
 Repeat if borderline
 Screening at birth
 CAH
 Controversial
 Many false positives.
 Due to start in California sometime soon
 Repeat and refer.
 Monitor electrolytes
Thank You