Endocrine Review

A. Makbul Aman Mansyur

Organs of the Endocrine
1. Pituitary gland
2. Hypothalamus
(neuroendocrine)
3. Pineal gland
4. Thyroid gland
5. Parathyroid gland
6. Thymus gland
7. Adrenal gland
8. Pancreas (also has
exocrine function)
9. Gonads (testes or
ovaries - also have
exocrine functions)
PITUITARY GLAND
What is a pituitary?
Pituita: Mucus
Former Belief That Pituitary Gland
Secretes Mucus

TWO PARTS :
ANTERIOR---ADENOHYPOPHYSIS
POSTERIOR--NEUROHYPOPHYSIS

Pituitary Hormones
Anterior Pituitary
Testosterone
Estradiol
FSH & LH
Growth
Hormone
ACTH
Cortisol
TSH
T
3
T
4
Prolactin
Posterior Pituitary
IGF-1
Oxytocin ADH
Hypothalamic Releasing
Hormone
Corresponding Anterior
Pituitary Hormone(s)
Gonadotropin Releasing
Hormone (GnRH)
Luteinizing Hormone (LH)
Follicular Stimulating
Hormone (FSH)
Growth Hormone
Releasing Hormone (GRH)
Growth Hormone (GH)
Corticotropin Releasing
Hormone (CRH)
Adrenocorticotropic
Hormone (ACTH)
Thyrotropin Releasing
Hormone (TRH)
Thyroid Stimulating
Hormone (TSH)
Dopamine
Prolactin (PRL)
Green = stimulatory
Red = inhibitory
Diseases of the Posterior
Pituitary
Syndrome of inappropriate antidiuretic
hormone secretion (SIADH)
Hypersecretion of ADH
Clinical manifestations are related to enhanced renal water retention,
hyponatremia, and hypoosmolarity
Diabetes insipidus
Insufficiency of ADH
Polyuria and polydipsia
Partial or total inability to concentrate the urine
Neurogenic
Insufficient amounts of ADH
Nephrogenic
Inadequate response to ADH
Vasopressin ( ADH)
Control
Increased plasma
osmolality
Decreased blood
pressure
(Baroreceptors)
PaO
2
PaCO
2
(cortisol Sex steroids
angiotensin II)
Action
Collecting ducts
permeability for
H
2
O
reabsorbtion of free
water
Vasoconstriction

Oversecretion of ADH even with low osmolalities
(Schwartz-Bartter Syndrome)
ADH Syndromes -
Overproduction
Syndrome of
Inappropriate
ADH (SIADH)
Na
+
(<130mmlol/l)
Plasma osmolality
(<270mOs/l)

Urine osmolality
(>100mOs/l)
Urine Na+
(>20mmol/l)

Brain injury/infection
Guillian Barre
Lung cancer/infection
Drugs
Hypothyroidism
Porphyria

Test
Plasma and urine
osmolality
Plasma and urine
electrolytes
Syndrome of Inappropriate
Antidiuretic Hormone (SIADH)
Etiology:
Bronchogenic carcinoma
Severe pneumonia
Pneumothorax
Head injury
Brain surgery
Brain tumor
Meningitis
Pituitary-stimulating drugs
Vincristine
Phenothiazines
Tricyclic antidepressants

Signs & Symptoms of SIADH

Confusion
Muscle weakness
lethargy
Decreased urine output
Increasing urine concentration
Weight gain
Seizures

Clinical Features SIADH
Confusion, nausea, irritable - progressing to seizures and coma
Dilution effect leads to Hyponatraemia (usually <125 mmol/l)
Biochemistry: low plasma - sodium, osmolality, and high urine
osmolality.
Normal blood pressure, serum potassium, renal function and
adrenal function.


SIADH
DIAGNOSTIC TESTS:
Serum sodium- decreased
Serum calcium- decreased
BUN and creatinine- normal
Plasma osmolality- decreased
Urine osmolality- elevated

Management of SIADH

Eliminate underlying cause
Restrict fluids (500-1000 mls/day )
Strict intake & output
Diuretics
Daily weights
Frequent serum & urine chemistries
Frequent neurological checks
Demeclocycline (Demethylchlortetracycline -
tetracycline antibiotic) administered - inhibits ADH
action on renal tubules
Severe cases - Hypertonic saline

ADH Syndromes -
Underproduction
Diabetes Insipidus
Polyuria
Polydipsia
Na
+
Plasma osmolality
>295mOs/l
Urine osmolality
<300mOs/l
Urine output
(>3 l/day)
Cranial
Genetic
Surgery
Injury infection
Drugs
Nephrogenic
Genetic (X)
Infection
Drugs
Test
Water deprivation test

Hyposecretion Posterior Lobe-
DIABETES INSIPIDUS
Causes: hyposecretion of ADH
Pituitary tumours
Infection
Trauma
intracranial surgery
Renal Disease
Some drugs
Hypotonic Polyuria (10-15+ litres/day), nocturia, and
compensatory polydipsia - severe dehydration
stroke (CVA)
Hodgkins disease
tuberculosis

CLASSIFICATIONS OF DI
NEPHROGENIC:
Inherited disorder where kidneys do not respond to ADH; no deficiency
in hormone
CRANIAL ( CENTRAL )
PRIMARY:
Defect in pituitary or hypothalamus; lack of ADH production or secretion
SECONDARY:
Tumors of pituitary or hypothalamus; trauma, infection, surgery,
metastasis of oat cell cancer in lung or breast
DRUGS:
Any drug that might interfere with kidneys response to ADH; lithium
carbonate (psych- manic/depressive)
PSYCHOGENIC:
Client ingests large quantities of water, usually 5 liters or more which in
turn depresses ADH production/secretion
Signs & Symptoms of
Diabetes Insipidus
Polyuria
Specific gravity
1.001.005
Polydipsia
Dehydration
Dry skin
Constipation
Confusion
Insatiable thirst
Urine osmo less
than plasma
osmo
Urine without
sugar or albumin

Investigations:
Diabetes Insipidus
Urine (low/dilute - 100 mosmol/kg)/plasma
Specific Gravity of Urine : 1.003 or less
Serum sodium: moderate increase upto 150
mmol/l when individual has free access to water
If no free access to water there is an increase in
the plasma osmolality and sodium concentration
(160-170 mmol/l)
8 Hour Water depletion test (Dashe test )
Prolonged water depletion test
Treatment for Diabetes
Insipidus
Fluid replacement
Accurate intake & output
DDAVP (Desamino-D-Arginine Vasopressin)-
- 10-20 micrograms 1-3 times/day via intranasal
route for maintenance or 1-2 mcg post-operative.
or IM/SC route at 1/10th of dose.
Correct underlying intracranial problem
Wear Medic Alert bracelet
Chlorpropamide (Diabinese), thiazide diuretics for
mild neurogenic DI
Clofibrateantidiuretic effect
20
Diseases of the Anterior
Pituitary
- function: Hyperpituitarism
- function: Hypopituitarism
Hypopituitarism
Pituitary infarction
Sheehan syndrome
Hemorrhage
Shock
Others: head trauma, infections, and tumors
Panhypopituitarism
ACTH deficiency, TSH deficiency, FSH and LH deficiency, GH
deficiency



Sheehans Syndrome
Pituitary infarction associated with uterine hemorrhage at time of delivery
Symptoms: absence of lactation, amenorrhea, fatigue, cold intolerance

Empty Sella Syndrome
An intrasellar extension of the subarachnoid space resulting
in compression of the pituitary gland and an enlarged sella
turcica that may be associated with galactorrhea and
hyperprolactinemia.
Radiologic finding of decreased pituitary gland volume
Only 10% of patients have hypopituitarism

Dwarfism
Insufficient secretion of growth hormone (GH)
during childhood that limits growth
Body parts usually correctly proportioned, normal
mental development
Usually accompanied by deficient secretion of
other anterior pituitary hormones additional
symptoms
Treatment with hormone therapy
hipopituarisme
Deficiency of growth hormone early in life leads to pronounced
inhibition of longitudinal growth, resulting in dwarfism. The
interrelationship between the pituitary and the thyroid is demonstrated
by the concomitant hypothyroidism secondary to deficiency of
thyrotropic hormone. Therefore, growth is not only stunted but the
development of secondary ossification centers is noticeably delayed,
and the epiphysial and apophysial growth plates remain open late in
adult life, although they do ultimately close in old age. The cranial
sutures remain widely open into adult age. The sella turcica may show
widening, if the tumor was intersellar, or an aperture may remain on the
floor of the endocranial bones. The skeleton is gracile in dimensions,
the cortices are thin, and the spongiosa porotic and sparse. Although
growth plates may remain, the metaphysial surface is usually closed by
a thin layer of bone, an indication of arrested growth.
25
Diseases of the Anterior
Pituitary
Hyperpituitarism
Commonly due to a benign, slow-growing pituitary adenoma
Manifestations
Headache and fatigue
Visual changes
Hyposecretion of neighboring anterior pituitary hormones
Hypersecretion of growth hormone (GH)
Acromegaly
Hypersecretion of GH during adulthood
Gigantism
Hypersecretion of GH in children and adolescents

Hypersecretion of Growth
Hormone (GH)
Acromegaly
Rare disease
Increased morbidity/mortality
Gradual development; 5-15 year delay in diagnosis
Symptoms: acral overgrowth, sweating, diabetes,
HTN, headache, etc.
Diagnosis: elevated IGF-1 on two occasions, MRI
brain
Treatment: surgery

Causes of Death
Cardiovascular- 38 to 62 percent
Respiratory- 0 to 25 percent
Malignancy- 9 to 25 percent
Acromegali
Systemic effects of GH/IGF-I excess
Acral enlargement
spade like hands rings too small
Inc shoe size
macroglossia
carpal tunnel syndrome
Increased skin thickness
Increased sweating
Skin tags and acanthosis nigricans
Change appearance
inter-dental spacing
Visceral enlargement
Acromegaly - Signs and
Symptoms
GH Excess
Enlargement of hands and feet
Thick skin
Skin tags
Sweating
Sleep Apnea
Carpal Tunnel Syndrome
Glucose intolerance
Osteoarthritis
Colonic Polyps
Tumor-related
Headache
Visual field defect
Loss of pituitary function
Gonadotrophins
TRH - hypothyroid
ACTH - Addisons

Impaired fasting glucose, Impaired glucose tolerance, Diabetes mellitus
Insulin resistance, Reduced total cholesterol and increased triglycerides
Increased nitrogen retention
Metabolic features :
Clinical Findings of Acromegaly
http://www.endotext.com/neuroendo/neuroendo5e/neuroendoframe5e.htm
Symptoms and signs at
presentation
Overall prevalence (%)
Facial change, acral enlargement, and soft-tissue
swelling
100
Excessive sweating 83
Acroparesthesiae/ carpal tunnel syndrome 68
Tiredness and lethargy 53
Headaches 53
Oligo- or amenorrhea, infertility 55*
Erectile dysfunction and/or decreased libido 42#
Arthropathy 37
Impaired glucose tolerance/ diabetes 37
Goiter 35
Ear, nose throat and dental problems 32
Congestive cardiac failure/ arrythmia 25
Hypertension 23
Visual field defects 17
* percentage of female patients
# percentage of male patients
Complications of Acromegaly
Cardiovascular
Ischemic heart disease
Cardiomyopathy
Congestive heart failure
Arrhythmias
Hypertension

Respiratory
Kyphosis
Obstructive sleep apnea

Metabolic
Diabetes mellitus/IGT
Hyperlipidemia
Neurologic
Carpal Tunnel syndrome
Stroke

Neoplastic
Colorectal
(Breast and prostate - uncertain)

Musculoskeletal
Degenerative arthropathy
Calcific discopathy, pyrophosphate
arthropathy
http://www.endotext.com/neuroendo/neuroendo5e/neuroendoframe5e.htm
Diagnosis of Acromegaly
Random GH not useful
Insulin like growth factor 1 (IGF-1)
best for screening
Oral glucose GH suppression testing
gold standard to confirm diagnosis

Skin Tags
Acromegaly
Frontal Bossing
Chin Protrusion
Bone and Soft Tissue Manifestations
of Acromegaly
Acromegaly: Large Hands
Gigantism
Oversecretion of GH during childhood
Height may exceed 2 M
Rare. Results of a pituitary gland tumor.
May have over-secretion of other pituitary
hormones.
Often have several metabolic
disturbances.
38
Diseases of the Anterior
Pituitary
Hypersecretion of prolactin
Caused by prolactinomas
Most common of functional pituitary adenomas
(25-30% of all pituitary adenomas)
In females, increased levels of prolactin cause
amenorrhea, galactorrhea, hirsutism, and
osteopenia
In males, increased levels of prolactin cause
hypogonadism, erectile dysfunction, impaired
libido, oligospermia, and diminished ejaculate
volume
Hyperprolactinemia: Clinical
Presentation
Women:
Amenorhea 57-90 %
Oligomenorrhea
10-28 %
Regular menses
9-15 %
Galactorrhea 30-80 %
Headache 40 %
Visual field defect<25 %
Hirsutism 19 %
Men:
Decreased libido 75-100 %
Impotence 68-100 %
Headache 70 %
Visual field defect 36-70 %
Galactorrhea 10-30 %
Gynecomastia 4-50 %

Not all hyperprolactinemic patients display galactorrhea and galactorrhea can be
seen with normal prolactin level
Remember that there are four main known causes of
hyperprolactinemia
1. Pregnancy
2. Drug use
3. Hypothyroidism
4. Pituitary tumors
Remember that it is not essential to treat asymptomatic
hyperprolactinemic women but follow-up is a must.
Remember that the problem is never over once pregnancy occurs
REMEMBER: Not all hyperprolactinemia is due to a prolactinoma
About 3% to 5% of individuals with hyperprolactinemia have
hypothyroidism, and thus TSH, the most sensitive indicator
of hypothyroidism, should be measured in all individuals with
hyperprolactinemia.

Management
Indications for treatment include the presence
of significant symptoms such as :
1. Disabling galactorrhea,
2. Amenorrhea, and infertility;
3. Presence of visual field defect and cranial
nerve palsy; and
4. Abnormal test results such as detection of a
pituitary tumor,
5. Diminished libido,
6. Osteopenia, or osteoporesis.
Medical treatment
1. Suppressing prolactin secretion and its clinical
and biochemical consequences,
2. Reducing the size of the prolactinoma, and
3. Preventing its progression or recurrence.

Pharmacotherapy of Prolactinomas :
Dopamine agonists are treatment of choice for most
prolactinomas
Choices include Bromocriptine, Pergolide and Cabergoline
Side effects include: postural hypotension, dizziness,
nasal stuffiness, GI side effects.


Medical treatment goals
Surgical Care
General indications for pituitary surgery
include :
1. Patient drug intolerance,
2. Tumors resistant to medical therapy,
3. Persistent visual-field defects in spite of
medical treatment, and
4. Patients with large cystic or hemorrhagic
tumors.
Trans-sphenoidal surgery
is the conventional procedure.
THYROID GLAND
Evaluation of Thyroid Function
TSH very sensitive and specific marker of
thyroid function
TSH + T4 = hyperthyroidism
TSH + T4 = hypothyroidism
Radionuclide scans 123I (RAI)
Nonfunctional area cold nodule
Hyperfunctional area hot nodule
If hyperthyroidism present then
uptake Graves Disease
Uptake exogenous thyroid usage
Thyroiditis
A nodule which concentrates iodine hot is very unlikely to be
malignant
Nodule can be detected and classified as cystic, solid or mixed

Hyperthyroidism
= a hypermetabolic state, caused by increased levels of T3 & T4.
Signs and symptoms: thyrotoxicosis
Stimulates heart, protein synthesis, breakdown>build up leading
to negative nitrogen balance (degradation); hyperglycemia;
increased fat metabolism
Effects: nervousness, warm moist skin, fine tremors, palpitations,
exophthalmos, weight loss, heat intolerance, muscle atrophy & weakness,
osteoporosis, amenorrhea, tachycardia, lid lag or stare, goiter
(Graves disease), atrial fibrillation
Most Common Causes: Graves disease, toxic multinodular goiter, toxic
adenoma
Less Common Causes:
- thyroiditis, struma ovarii, toxic carcinoma
- TSH-secreting pituitary adenoma
- overtreatment with thyroid hormone tablets (factitious hyperthyroidism)







Thyroid - Hyperthyoidism

Graves disease: toxic diffuse goiter

Most common cause hyperthyroidism
Strikes women, 20-30.
Multisystem syndrome, affecting eyes, skin, bones
No sure cause: autoimmune disorder
Generally emotional upset precedes symptoms
Has heredity component
Assessment:
Increase appetite but slight wt loss
Dyspnea
Decreased heat tolerance
Menstruation may decrease or stop
Increased bowel movements or diarrhea
Nervous, irritable, restless
Speak rapidly; laugh inappropriately
Exopthalamus (BUG-EYE)
Moist skin, thinning hair, elbows red; clubbing of nails (Plummers nails),
hyperpigmentation (vitiligo- milk-white patches)
Tremors, weakness
Tachycardia, atrial fibrillation; widened pulse pressure
Fine, soft hair; moist skin
Hyperactive deep tendon reflexes

Thyrotoxicosis (Graves Disease)
Abnormal protrusion of the eyes.
Graves Diseases
Diagnostic tests:
Elevated T
3
, T
4
and TSH Below normal
No response to TRH
Thyroid scan
Interventions: ( drugs, RAI, Surgery )
Record vital signs
Rest, cool environment
Drugs to reduce hormone:
PTU
methimazole
Iodine-radioactive; cells are destroyed
B-blockers : not used on clients with asthma or heart disease
Watch for agranulocytosis: fever, sore throat, rash
Treatment does not correct infiltrative opthalopathy; use tears,
elevate head, diuretics for edema; prednisone


Hyperthyroidism
Thyroid storm:
Crisis situation- usually caused by Graves
Life-threatening
Uncontrolled hyperthyroidism
Develops quickly and triggered by stress; over-
palpation of gland
Fever, tachycardia, systolic hypertension, GI,
restlessness, confused, psychotic
Even with treatment, 25% mortality rate
HYPOTHYROIDISM
- Deficiency in thyroid hormone = a hypometabolic state caused by deficiency
of T3 & T4.
- Goitre: iodine deficiency. No goitre: TSH deficiency
Leads to low metabolism with build-up of metabolites
Metabolites with water accumulate within cells, cause edema, called
myxedema
Myxedema coma: rare but can occur; heart becomes flabby, chambers
increase in size, CO decreases; life threatening; high mortality rate
3 TYPES:
HYPOTHYROIDISM: adult onset; tissue destruction is most probable cause
CRETINISM:
Profound hypothyroidism in infants, all developmental aspects are retarded,
severe brain damage can occur
JUVENILE HYPOTHYROIDISM:
Begins during childhood, Hashimotos disease, caused by drugs,
autoimmune
Affects growth and sexual maturation

HYPOTHYROIDISM
SIGN AND SYMPTOMS :
Changed sleeping habits (increased), Lethargy, wt gain, Cold
intolerance, Dyspnea, Constipation, Menorrhagia, Muscle aches,
Anorexia, Lack of expression, Cool, dry, skin rough and thick,
dry hair, coarse, enlarged tongue, Speech slow and deliberate
with hoarse voice, Impotence and infertility, decreased blood
pressure; bradycardia; dysrhythmias; decreased urinary output

Diagnostic tests:
Below-normal T
3
& T
4

Above-normal TSH
Above-normal TRF
Above-normal creatinine phosphokinase
Anemia

Thyroid - Hypofunction

HASHIMOTOS THYROIDITIS
- MCC of hypothyroidism in areas where iodine intake is adequate
Clinically:
- seen predominately in middle-aged women
- hypothyroidism with painless enlargement of the gland
- may have transient thyrotoxicosis early on
- familial predisposition, associated with HLA-DR3 or HLA-DR5
Pathogenesis:
- defective function of thyroid-specific suppressor T cells
emergence of helper T cells reactive with thyroid antigens
- helper T cells stimulate B cells to secrete antithyroid antibodies,
directed against: thyroid peroxidase, TSH-receptors, iodine
transporter, & thyroglobulin, etc.
- thyroid injury is mediated by complement fixing cytotoxic
antibodies, ADCC & CD8+ cytotoxic cells
HYPOTHYROIDISM
Interventions:
Requires life-long replacement hormone
Synthetic usually used T
4
(Levothyroxin, euthyrox )
Start with lowest dose possible and work way up
every 1-3 weeks
With known cardiac problems, always use lowest
dose possible
T
3
(Cytomel) has more rapid effect.
Make sure client knows to continue with meds even if
he feels better
Avoid sedation if possible
THYROIDITIS
Inflammation of thyroid
Three types:
Acute: bacterial; pain, malaise, fever, dysphagia; treat with antibiotics
Subacute: viral infection; fever, chills, dysphagia, pain, hard &
enlarged gland; treat symptoms; antivirals
Chronic: (Hashimotos)- auto immune, invade thyroid with antibodies
and lymphocytes causing tissue destruction; treat with thyroid
hormone
Administer thyroid hormones; surgery; promote comfort and teaching
Acut Thyroiditis
Self-limited
B-blockers for adrenergic Sign

PARATHYROIDS
The parathyroid glands are embedded in the posterior surface of the thyroid gland.
Usually 4 parathyroid glands a superior and inferior on each of the thyroids
lateral lobes.
PARATHYROIDS
Parathyroid hormone corrects calcium deficiency by promoting
calcium conservation by kidneys, stimulating calcium release by
bone, enhance calcium absorption from GI, & reduce serum
phosphate levels.
Works on negative feedback control
Affects bones, kidneys, and intestine
In Bones: inhibits osteoblast (build bone) and stimulates osteocytes
and osteoclasts to resorb bone and release calcium and phosphate
ions into the blood.
In kidneys, causes calcium to be reabsorbed with release of
phosphorus
Stimulates kidneys to convert Vit D to a metabolite that allows for
PTH to work on bone
Calcitonin from thyroid causes inhibition of Ca++ release from bones
Increases blood calcium concentration and decreases blood
phosphate ion concentration
Intestine: stimulates calcium absorption from food in the intestine,
increasing blood calcium concentration
Hyperparathyroidism

3 Type :
Primary:
Faulty PTH regulation; adenoma, genetics, CA, radiation,
hyperplasia; occurs more commonly in women, 35-65
Secondary:
Compensatory response to defective homeostasis, chronic
renal failure, malabsorption disorders
Tertiary:
Compensates for secondary malfunction to primary, leading
to overgrowth of gland and overproduction and secretion

All three lead to increased calcium and
decreased phosphorus

HYPERPARATHYROIDISM
Sign and Symptoms :
Urine calcium increase and kidneys fail to concentrate urine
Phosphorus excretion increases
Enhances sodium, potassium, amino acids, bicarbonate
(acidosis leading to excretion of Ca
++ )

Polyuria
Renal calculi
Bone demineralization (breakdown):Bone pain, Pathologic
fractures, Cystic bone disease
Others Sign : Weakness, wt. loss, fatigue, depression, Renal colic
pain, back pain, Hematuria, renal calculi, cholelithiasis, Anorexia,
vomiting, constipation, Peptic ulcer (stimulates gastric HCL),
Increase heart contractility; decreased automaticity, Hypertension,
Depressed reflexes- hyporeflexia, Confusion, irritability, mood
swings

Hyperparathyroidism : Diagnostic Test

Serum PTH: elevated
Calcium: elevated (>10.5mg/dl; 5.2mEq/L
Kidney stones
Phosphorus: decreased
X-rays; CT; MRI: look at bone density and
demineralization
PTH infusion test: (Ellsworth-Howard excretion test);
give IV PTH, hourly urine samples looking for
phosphorus
Calcitonin stimulation test: if cancer suspected; use
calcium gluconate

Hyperparathyroidism : Intervention
- Surgery
- Stabilize calcium levels prior to surgery
Medical treatment:
Rehydration with isotonic fluids
Diuresis
Restrict intake of calcium (thyazides and Vit D.
Monitor EKG
Drugs:
Phosphates: Neutra-phos
Calcitonin: IV; IM- decrease release from skeletal areas; increased
excretion by kidneys
Calcium chelators ( bind calcium) Plicamycin: mithramycin; cytotoxic
agents; watch for thrombocytopenia
Steroids: inhibit Vit D
Estrogen
Alpha & beta blockers
cimetidine

Hypoparathyroidism

Too little PTH leading to decreased calcium and
increase phosphorus
3 types
Iatrogenic:
Most common, resulting from surgery of neck removing glands,
radiation, or other trauma
Idiopathic:
Early onset and late onset; autoimmune; genetic causes of
absent glands, pernicious anemia, ovarian failure
Functional:
Long term hypomagnesemia causes this (alcohol,
malabsorption)
Hypoparathyroidism
Sign and Symptoms :
Neuromuscular problems, increased excitability, tetany, muscle
cramps, tingling, numbness, hyperreflexia
Tetany leads to anxiety; leads to hyperventilation; leads to
hypocapnia and alkalosis, which worsens hypocalcemia
Seizures, laryngeal spasms
Personality changes
Nausea, vomiting
Dysrhythmias, decreased contractility, reduced CO
Cataracts, dry skin, scaly, coarse
Alopecia
Bands or pits on teeth
Diagnosis of
Hypoparathyroidism
Signs of tetany
Trousseaus sign and Chvosteks sign
Diagnostic tests:
Serum calcium: low
Serum phosphorus: high
Serum magnesium: normal to low
Serum PTH: low
Urinary creatinine: low
Urinary excretion of calcium: high
- Increased bone density on x-ray


PARATHYROID
Interventions:
Treatment focuses on preventing tetany and
correcting hypocalcemia
IV calcium gluconate or calcium gluconate
Do not use saline, promotes calcium and sodium excretion
Avoid bicarbonate, cause precipitation
Vit D and calcium supplements
Ergocalciferol (Vit D
2
); Rocaltrol; may use combined therapy of
oral and IV initially
Need 1 gram of calcium daily if using Vit D
Life-long therapy
Emergency airway if laryngeal spasms occur
Foods high in calcium but low in phosphorus- milk, yogurt,
processed cheese.











Structure:
Adrenal medulla: central
portion. Irregularly shaped
cells organized in groups
around blood vessels.
Connected with the
sympathetic division of the
autonomic nervous system.
Modified post-ganglionic
neurons
Adrenal cortex: outer
portion. Epithelial cells in
layers. Well supplied with
blood vessels.
Sits atop each kidney and is embedded in the
mass of adipose tissue that encloses the kidney
ADRENAL GLAND
- Composed of two distinct units: steroid secreting cortex &
catecholamine producing medulla
- In the adult, the normal adrenal weighs 4 gm.
- The cortex consists of three functional zones:
1 - zona glomerulosa
2 - zona fasciculata (75% of the cortex)
3 - zona reticularis
- The cortex secretes three types of steroid hormones:
1 - mineralocorticoids (aldosterone) - zona glomerulosa.
2 - glucocorticoids (cortisol) - zona fasciculata mainly.
3 - sex steroids (testosterone) - zona reticularis mainly.
Table Adrenal gland: characteristics
Alterations of Adrenal Function
Disorders of the adrenal cortex
Hypersecretion of adrenal androgens and estrogens
Feminization
Virilization
Cushing disease
Excessive anterior pituitary secretion of ACTH
Cushing syndrome
Excessive level of cortisol, regardless of cause
Disorders of the adrenal medulla
Adrenal medulla hyperfunction
Caused by tumors derived from the chromaffin cells of the
adrenal medulla
Pheochromocytomas
Secrete catecholamines on a continuous or episodic basis



DISEASES OF ADRENAL CORTEX
Hyperfunction (hyperadrenalism):
- Cushings syndrome
- Hyperaldosteronism
- Adrenogenital syndromes
Hypofunction (hypoadrenalism):
- Acute (e.g. Waterhouse-Friderichsen Syndrome)
- Chronic:
primary (due to adrenal cortical insufficiency, e.g. Addisons
disease)
secondary (due to ACTH deficiency)
tertiary (rarely - due to hypothalamic CRH deficiency).
Cushings syndrome: hypercortisolism

Cortisol excess
Affects more women than men
Primary:
Usually a neoplasm
Secondary:
Pituitary or hypothalamus disorder causing increased ACTH;
adrenal hyperplasia
Iatrogenic:
Excessive use of steroids (prednisone)
Artifically increases cortisol, suppresses ACTH, causing adrenal
atropy
S/S are of hyperfunction
ADRENAL GLAND Cushings
Assessments:
Fatigue, muscle wasting
Frequent infections, slow wound healing
Suppressed immune response ( can mask S/S); kill lymphocytes
Truncal obesity, buffalo hump, moon-shaped face, scrawny arms and
legs (PICKLE WITH LEGS)
Fragile skin, purplish striae on abdomen, buttocks, breasts, bruises
Masculinization in women, hirsutism (increased hair growth), acne
Hypertension
Osteoporosis
Labile emotions
Abnormal sleep patterns
Nitrogen, carbohydrate, and mineral metabolism
Elevated blood glucose
Central Obesity in Cushings
Disease
Williams Textbook of Endocrinology. 8
th
Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
Buffalo Hump in
Cushings Disease
Orth, D. UpToDate
Striae in Cushings
Disease
Proximal Muscle Wasting
Cushing Disease
ADRENAL GLANDS CUSHINGS
Diagnostic tests:
Cortisol: high with no circadian variation
Urinary levels of steroid metabolites: high
RBC and granulocytes: high
X-rays, MRI, CAT scans
Dexamethasone suppression test: give 1 mg
at night, test at 8am; high level
ADRENAL GLAND CUSHINGS
Interventions:
Treat underlying cause; stop steroids
Remove tumors of pituitary or adrenalectomy
( uni or bi lateral)
Drugs:
Mitotane to inhibit cortisol synthesis ( watch for
adrenal crisis!!
Cyproheptadine: ACTH inhibitor
Aldactone: mineralocorticoid antagonist to relieve
hypertension and hypokalemia
ADRENAL GLAND CUSHINGS
Complications:
Fluid and e-lyte imbalances
Hypertension: Na
+
and water retention
CHF: excess volume in compromised heart
Hypokalemia
Ventricular dysrhythmias: due to CHF and
hypokalemia
Increased risk for infections & fractures
Skin breakdown
PRIMARY HYPERALDOSTERONISM
= excessive secretion of aldosterone independent of renin-
angiotensin system.
Features: hypervolemia, hypokalemia, hypertension, low renin
Causes:
- MCC is aldosterone-secreting adenoma (Conns syndrome) in
80% of cases
- Bilateral idiopathic hyperplasia (? due to an abnormal
secretagogue)
- Glucorticoid-suppressible hyperaldosteronism: hybrid cells
produce both cortisol & aldosterone, aldosterone under
influence of ACTH, suppressible by administration of
dexamethasone
Prognosis: adenomas are curable by surgery.
CHRONIC ADRENOCORTICAL
INSUFFICIENCY
Primary (adrenal) or secondary (hypothalamic/pituitary):
Primary (Addisons disease): MCC: autoimmune adrenalitis;
tuberculosis, metastatic cancers ( destruction of 90% of
the cortex) decreased cortisol & aldosterone, with feed-
back elevation of ACTH (+ MSH) hyperpigmentation of
skin, K
+
, Na+, BP, weakness, anorexia, N&V,
hypoglycemia

Secondary: to hypothalamic or pituitary lesions associated with
decreased ACTH bilateral adrenal cortical atrophy,
sparing the zona glomerulosa (skin color is pale and
aldosterone is normal, i.e. no sodium or potassium
abnormalities).
ADRENAL GLAND
INSUFFICIENCY: ADDISONS
Suppressed adrenocortical function and hormones
May precipitate adrenal crisis: life-threatening
Primary:
Addisons- rare, chronic disorder
90% gland usually destroyed before symptoms appear
Secondary:
Reduced ACTH secretion caused by pituitary disease or
exogenous steroid administration; more common
Impairs stress response by reducing cortisol,
aldosterone, and androgens

ADRENAL GLAND ADDISONS
Assessments:
Muscle weakness and fatigue (especially during stress)
Nausea, vomiting, diarrhea, abdominal pain
Salt craving
Anxiety, restlessness, irritability, and confusion
Orthostatic hypotension
HYPOGLYCEMIA & HYPERKALEMIA
Hyperpigmentation (ONLY PRIMARY DISEASE HAS THIS)
Knees, elbows, nipples, palm creases, scars( bronzed, dirty tan)
Small black freckles on neck, face; bluish splotches on mucous
membranes
Addisons Disease
Clinical Presentation:
Looks chronically ill,
weight loss, lethargy,
weakness, low libido
Dehydration
Creases in elbows,
knees and lips
Nausea, vomiting,
chronic abdominal pain
Muscle cramps
Hyper/hypo-
pigmentation
(unilateral, patchy)

Hyperpigmentation of lip
Hyperpigmentation in Addisons Disease

Diagnostic Tests for Addisons
Disease
Low levels adrenocortical hormones in blood or urine plasma
cortisol
a.m. 7-28 mcg/dl
p.m. 2-18 mcg/dl

ACTH injection fails to cause rise in plasma cortisol

Suggestive of disease
hypoglycemia
hyponatremia
hyperkalemia
Leukocytosis, hematicrite
BUN elevated; hematocrit elevated


ADRENAL GLANDS ADDISONS
Interventions:
Lifelong therapy with replacement
Drugs:
Cortisone: twice daily, increase dose for stressful times
Florinef: aldosterone replacement
Salt food liberally
Avoid fasting
Eat high carbs and proteins
Always wear medic alert identification
Carry emergency kit with 100mg hydrocortisone for injection
Prevent acute exacerbations
Avoid salt and fluid restriction with diuretics; may lead to crisis
ADRENAL GLANDS
Complications:
Adrenal crisis: due to insufficiency; can occur
gradually or abruptly (acute adrenal insufficiency)
Potentially lethal
Occurs in individuals who dont respond to therapy;
increased stress without increased meds; abrupt
corticosteroid withdrawal
ALWAYS WITHDRAW STEROIDS THERAPY
GRADUALLY
ADRENAL GLANDS ADRENAL
CRISIS
Treatment:
Restore volume with D
5
or NS
Be sure to assess fluid status frequently
Cortisol q 6 hr. (Solu-Cortef IV): if given with
saline, proves adequate to replace
Aldosterone
Do not give methyleprednisolone (Solu-
Medrol: lack mineralocorticoid effects)
Reduce anxiety
94
Adrenal Medulla
(part of autonomic nervous system)

Releases:
epinephrine
norepinephrine


Stimulated by:
fear
anger
stress
hemorrhage
hypoxia
hypoglycemia

ADRENAL GLANDS
PHEOCHROMOCYTOMA
Rare, benign tumor; arises in medulla
Results in hypersecretion of epinephrine and
norepinephrine
Tumors appear more commonly on right side; middle-
aged women
Can occur with thyroidal cancer and
hyperparathyroidism-Sipples syndrome
Complications:
Severe hypotension
CVA
Heart problems
If left untreated, always leads to death

PHEOCHROMOCYTOMA
= neoplasm composed of chromaffin cells that secretes
catecholamines (0.1 - 0.3 % of all cases of hypertension)
The 10 % tumor:
10 % extra-adrenal
10 % familial
10 % in children
10 % bilateral in sporadic cases, but 70% bilat.in familial cases
10 % malignant in adrenal cases, but up to 40% malignant in
extra-adrenal cases
Clinical effects: hypertension (paroxysmal), tachycardia,
arrhythmias, tremors, sweating, sense of apprehension,
attacks can be fatal
Diagnosis: 24 hour urine for catecholamines; or metanephrines &
vanillylmandelic acid (VMA)
Pheochromocytoma

Signs & Symptoms
hypertension
tachycardia
excessive sweating
tremor
headache
Vertigo
blurred vision
flushing
tinnitus
dyspnea
anxiety
hyperglycemia


Diagnosis
Pheochromocytoma
Serum catecholamines
epinephrine 400 pg/ml
norepinephrine 2000 pg/ml
Urine 24 hr. test for
Vanillylmandelic acid (VMA)
Clonidine test
MIBG scintigraphy (CT,
MRI, US used to localize the
tumor)
EKG changes
Diagnostic tests may
precipitate a crisis!!!




PHEOCHROMOCYTOMA
Assessment:
Exaggerated flight or fight reaction
High blood pressure (Hallmark sign) 200/150
End-organ damage; CVA, heart disease, kidney damage
Orthostatic hypotension
Attack occurs with sporadic release of catecholamines (May
result from exercise, lifting, emotional distress, exposure to cold,
food, alcohol, sex, etc.
Pounding heart beat, deep breathing
Peripheral vasoconstriction
Hyperglycemia
anxiety
PHEOCHROMOCYTOMA
Interventions:
Alpha-blockage to control HTN (phenoxybenzamine)
Surgical removal (adrenelectomi)
Prior to surgery, drugs to reduce the excessive adrenergic action
(2 weeks)
Receive plasma volume expanders
During surgery, receive Regitine, alpha-adrenergic blocker to
prevent hypertensive crisis
If unable to have surgery, may order drug, Demser, inhibits an
enzyme promoting norepinephrine synthesis
Avoid drugs like opiates, histamines, OTC cold medications
During attack, maintain bedrest, HOB elevated to at 30
0
to
reduce orthostatic hypotension
Signs & Symptoms of
Aldosterone Deficiency
Impaired Na+ conservation
weight loss
hypovolemia
low renal perfusion
increased renin production
weakness
postural syncope
Azotemia
Impaired renal secretion of K+ & H+
hyperkalemia
cardiac asystole
mild acidosis



Adrenal Sex Hormones
(adrenal androgens)

Mostly male, some converted to female
hormones (estrogens) in the skin, liver, and
adipose tissue.
Supplement supply of sex hormones from the
gonads
Stimulate early development of reproductive
organs.
Androgen Deficiency in Males
Diagnosis
- Appropriate symptoms ( libido, fatigue, erectile dysfunction)
- Serum testosterone below lower limits of normal
- Resolution of symptoms with androgen replacement

Erectile dysfunction inability to achieve an erection capable for
sexual intercourse at least 25% of the time

Treatment
Testosterone replacement: injections, patch, gel
Polycystic Ovarian Syndrome
Common 8-22% of population
Commonest cause of Hirsuitism
Pathogenesis
Hyperandrogenism
Insulin resistance
Presentation: acne, obesity (50%),
hirsutism, insulin resistance (40%),
abnormal lipids, menstrual dysfunction
Treatment: weight loss, metformin



Clinical Features (PCOS)
Oligomenorrhoea
Anouvulation
Hirstuism
Acne
Obesity
Hypertension
Glucose intolerance
Dyslipideamia
Reproductive Glands
Ovaries: produce
estrogens and
progesterone
Placenta: produces
estrogens,
progesterone, and
gonadotropin

Testes: produces
testosterone





TARGET TISSUES
PRL
SUMMARY OF THE MAJOR COMPONENTS OF THE
ENDOCRINE SYSTEM
TSH
CALCIUM
GH
ACTH
LH/FSH
GONADS LIVER
ADRENAL
CORTEX

PANCREAS

THYROID
INSULIN
GLUCAGON
STEROIDS
IGF-1
T3 +T4
STEROIDS
PTH




GLUCOSE





ANTERIOR LOBE
OF PITUITARY
POSTERIOR LOBE
OF PITUITARY


PARATHYROID
OXYTOCIN

MILK
BRAIN
BREAST
DIET
ADRENAL
CORTEX
VASOPRESSIN
FEEDBACK LOOPS
GHRH
GnRH
CRH
TRH
What Questions Can You
Answer For Me?
QUIZ




Name the hormones produced by the organs listed
below.
HYPOTHALAMUS
PITUITARY
ANTERIOR
POSTERIOR
THYROID
PARATHYROIDS



ADRENALS
CORTEX
MEDULLA
PANCREAS (2)
OVARY
TESTES
PLACENTA


What is diabetes
mellitus??


What is diabetes
insipidus??


Whats the diseases that caused by
Hypersecretion of ADH ?



What the diagnosis if you find:
Retention of water,hyponatremia
And hypoosmolarity ?


For patients diagnosed with
pituitary tumors, what is the
surgical treatment of
choice?

Hypersecretion of
GH in children and
adolescents ?

Which disease, caused by
a deficit in antidiuretic
hormone, results in
massive
diuresis and is treated with
vasopressin?


Deficiency of growth
hormone early in life will
leads ?

Whats the diseases that you will find : Skin tags
and acanthosis nigricans ?


What is the most
common disease
form of hypothyroidism?




What causes
Cushings
syndrome?

What diagnosis is made when a
patient has truncal obesity,
protein wasting, a moon face,
and osteoporosis?

Whats the diseases if
neoplasm composed of
chromaffin cells that secretes
catecholamines ?

What causes Conn
Syndrome?

Whats this ?
Virilization
This lady complains of fatigue, increasing
weight, memory loss and constipation
An elderly gentleman presents with confusion and
weight loss
What is the abnormaility in this 32 year old woman
with amenorrhoea and bitemporal hemianopia?
This lady presented with weight loss and
palpitations
This woman has presented with hair loss,
amenorrhoea and fatigue
Williams Textbook of Endocrinology. 8
th
Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
Hyperpigmentation of lip

Goiter
Bulge in the neck resulting from an
enlarged thyroid gland.
Toxic Goiter Simple Goiter
Hirsutism
Excess hair growth, especially in women.
Virilism
Masculinization of a female.
HYPOGONADISM
Hypogonadism
Hypopituitarism:

Infertility
Pallor
Low BMR
Intolerance to stress
Congenital Hypothyroidism
132
Patient #
Patient #
2
2
50 year old male
Chief complaints:
Fatigue
sweating of hands and
feet
Increasing shoe size
Joint pains
Headache
The End
Thank you for your attention