2. Endocrine Disorders
Etiology of Endocrine Disorders
• Hyposecretion or hypersecretion can occur in the:
– Hypothalamus/pituitary
– Hormone-producing gland
– Target tissue
• Etiology can be:
– Congenital
– Infectious
– Autoimmune
– Neoplastic
– Idiopathic
– Iatrogenic
3. Elevated or Depressed
Hormone Levels
• Failure of feedback systems
• Dysfunction of an endocrine gland
• Secretory cells are unable to produce, obtain, or
convert hormone precursors
• The endocrine gland synthesizes or releases excessive
amounts of hormone or not enough hormone
• Increased hormone degradation or inactivation
• Ectopic hormone release
• Target cell failure
4. Endocrine Disorders: Classification
• Endocrine disorders involving control by anterior
pituitary gland are classified as:
– Primary: intrinsic malfunction of the hormone-producing
target gland
– Secondary: malfunction of the hypothalamus/pituitary
cells that control the hormone-producing target gland
7. Diseases of the Anterior Pituitary
• Hypersecretion of growth hormone (GH)
– Acromegaly
• Hypersecretion of GH during adulthood
• (cause: GH-secreting pituitary adenoma)
– Gigantism
• Hypersecretion of GH in children & adolescents
8. Diseases of the Anterior Pituitary
Giantism:
Hypersecretion of growth hormone (GH)
(excess somatotropin [GH] BEFORE epiphyseal closure)
9. Diseases of the Anterior Pituitary
• Acromgaly:
Hypersecretion of growth hormone (GH)
(excess somatotropin [GH] AFTER epiphyseal
closure)
12. Hypothyroidism
• CONGENITAL HYPOTHYROIDISM (cretinism) is typically due to
thyroid dysgenesis
• Majority are PRIMARY, due to intrinsic dysfunction of the
thyroid gland
• PRIMARILY LYMPHOCYTIC THYROIDITIS (Hashimoto or
autoimmune thyroiditis)
Acquired
• Irradiation of the thyroid gland
• Surgical removal of thyroid tissue
• Iodine deficiency
13. Cretinism
Congential hypothyroidism: can be endemic (iodine
deficiency), genetic, or sporadic
Delayed bone maturation, puberty, mental
retardation, abdominal protrusion with umbilical hernia
14. A 3-month-old male was diagnosed with
congenital hypothyroidism. If left untreated, the
child would have:
A. mental retardation and stunted growth.
B. increased risk of childhood thyroid cancer.
C. hyperactivity and attention deficit disorder.
D. liver, kidney, and pancreas failure.
15. ETIOLOGY AND PATHOGENESIS:
Hypothyroidism:
Primary Hypothyroidism
• Iodine is essential for T3 and T4 synthesis
• Deficiency in iodine leads to lack of T3/T4 but does not affect
thyroglobulin levels
• Insufficient hormone available to inhibit secretion of TSH
• Increased TSH causes thyroid cells to secrete large amounts of
thyroglobulin, which leads to a goiter
19. ETIOLOGY AND PATHOGENESIS:
Hypothyroidism:
Secondary hypothyroidism is caused by defects in TSH
production and can result from:
• Severe head trauma
• Cranial neoplasms
• Brain infections
• Cranial irradiation
• Neurosurgical procedures
20. Clinical Manifestations
Infants Children/Adults
• Dull • Decreased basal metabolic rate
• Weakness, lethargy, cold
appearance, thick, protuberant
intolerance, decreased appetite
tongue, and thick lips result in
• Bradycardia, narrowed pulse
feeding difficulties
pressure, and mild/moderate weight
• Prolonged neonatal jaundice gain
• Poor muscle tone • Elevated serum cholesterol and
• Bradycardia, mottled extremities triglycerides
• Enlarged thyroid, dry skin, constipation
• Umbilical hernia
• Depression, difficulties with
• Hoarse cry
concentration/memory
• Menstrual irregularity
21. Hashimoto’s thyroiditis
• Chronic lymphocytic thyroiditis
• Infiltration by lymphocytes
• Destruction of thyroid by antibodies
• Goiter formation is common
• Can occur with other autoimmune diseases: Type 1 DM, vitiligo
22. CLINICAL FEATURES of Hashimoto’s Thyroiditis
• Onset of disease – 30-60 years of age
• 5 times more common in females than males
• Patients have T4 and TSH
• Patients have enlarged thyroid (goiter)
• Symptoms include:
– Dry skin, tiredness, weight gain, puffy face, intolerance to
cold, mild depression
• Treatment – thyroid hormone replacement
24. Myxedema
• Severe or prolonged thyroid deficiency
• Accumulation of glycosaminoglycans in
interstitial spaces
Myxedema
(coma)
• Sluggishness
• Cool
skin, ↑cholest
erol
25. DIAGNOSIS: Hypothyroidism
• Primary hypothyroidism will manifest as elevated
TSH
• Low levels of T3 and T4 may not occur until later in
the disease course
• Hypothalamic-pituitary dysfunction results in low
levels of TSH and T4
26. TREATMENT: Hypothyroidism:
• Treatment goal is return of euthyroid state
• Oral levothyroxine is used to replace or supplement
hormone production
• Resolution of symptoms occurs over weeks
• Intravenous levothyroxine used for myxedema coma
27. Hyperthyroidism
• Primary—autonomous
• Secondary—mediated through stimulation of TSH
receptors by substances such as TSH
• Autoimmune—related to TSH receptor antibodies
28. ETIOLOGY AND PATHOGENESIS: Hyperthyroidism
What causes Hyperthyroidism?
• Pituitary adenoma
• Thyroid carcinoma
• Autoantibodies that bind and stimulate TSH receptors on
the thyroid gland leading to a diffuse toxic goiter (Graves
disease)
• Ingestion of thyroid hormone preparations or excessive
iodides
29. CLINICAL MANIFESTATIONS: Hyperthyroidism
• Changes in
behavior, insomnia, restlessness, tremor, irritability, p
alpitations, heat intolerance, diaphoresis, inability to
concentrate that interferes with work performance
• Increased basal metabolic rate leads to weight
loss, although appetite and dietary intake increase
• Amenorrhea/scant menses
30. Graves Disease: autoimmune
most common form of hyerpthyroidism
Edema of orbit, exopthalmos, extrocular muscle weakness
32. Clinical Features of Graves’ Disease
• Onset of disease – 20-50 years of age
• 10 times more common in females than males
• Patients have goiter with thyroid gland 2-3 times normal
size
• Symptoms include:
– Nervousness, fatigue, weight loss; 50% have thyroid-
associated ophthalmopathy with eyelid retraction and
periorbital edema
• Treatment – anti-thyroid drugs, surgery, and radioactive
iodine ablation
33. Graves’ Disease: Diagnosis
• Diagnosis often made on clinical symptoms
alone
• Elevated T3 and T4; low TSH
– Why?
35. A 35-year-old female with Graves disease is
admitted to a medical-surgical unit. Lab tests
would most likely reveal:
A. high levels of circulating thyroid-stimulating
antibodies.
B. ectopic secretion of thyroid-stimulating
hormone (TSH).
C. low circulating levels of thyroid hormones.
D. stimulation of thyroid-binding globulin.
36. CLINICAL MANIFESTATIONS: Hyperthyroidism
Thyroid storm—form of life-threatening thyrotoxicosis
that occurs when excessive amounts of thyroid
hormones are acutely released into circulation
• Manifestations
– Elevated temperatures, tachycardia, arrhythmias
– Extreme restlessness, agitation, and psychosis
– Vomiting, nausea, diarrhea, and jaundice
37. DIAGNOSIS: Hyperthyroidism:
DIAGNOSIS
Primary hyperthyroidism will manifest as:
• Undetectable TSH levels
• Elevated serum T4 and T3
TREATMENTS:
• Symptomatic relief: Beta blockers
• Reduce circulating hormones: methimazole, propylthioricil
• More permanent treatment: surgical removal of thyroid, radioactive
iodine
38. TREATMENT: Hyperthyroidism
Treatment of thyroid storm
• Aggressive management to achieve metabolic
balance
• Antithyroid drugs are given followed by iodine
administration
• Beta-blockers to alleviate symptoms
• Antipyretic therapy
• Fluid replacement
• Glucocorticoids
39. Alterations of Thyroid Function: Table 40.2
Hypothyroidism Hyperthyroidism
Basal metabolic
rate
Sympathetic ANS
Weight
Temp tolerance
GI function
Cardio/Respiratory
function
Reproductive
Muscle tone
Appearance
General behavior
46. o By the time of the missile crisis, Kennedy was taking antispasmodics to
control colitis; antibiotics for a urinary tract infection; and increased
amounts of hydrocortisone and testosterone, along with salt tablets, to
control his adrenal insufficiency and boost his energy.
47. Adrenocortical Insufficiency
• SECONDARY: Hypothalamic-Pituitary
Dysfunction
– usually iatrogenic, related to corticosteroid
therapy, which suppresses ACTH, CRH
– May also occur due to damage of the anterior
pituitary or hypothalamus by
tumors, infection, radiation, postpartum
necrosis, trauma, or surgery
48. Adrenocortical Insufficiency
Addisonian crisis/acute adrenal insufficiency
• Life-threatening condition caused by inadequate
levels of glucocorticoids and mineralocorticoids in
circulation
• May occur with acute withdrawal of corticosteroids
or due to periods of stress or trauma
49. Adrenocortical Insufficiency
Clinical manifestations
• Early signs include:
– anorexia,
– weight loss
– weakness
– malaise
– apathy
– electrolyte disturbances
– hyperpigmentation of skin
• Diminished vascular tone, reduced cardiac
output, inadequate circulating blood volume; can
lead to cardiovascular collapse
50. Adrenocortical Insufficiency
Diagnosis
• Patient history and physical exam, decreased plasma cortisol
levels
• ACTH provocation test may be administered
• Abdominal CT/MRI may be performed to evaluate the size of
the adrenal glands
Treatment
• Replacing the absent or deficient hormones in a manner that
mimics natural production
• 2/3 of the daily dosage is given in the morning and 1/3 in the
evening
• Treatment of adrenal crisis
– Intravenous glucocorticoids
51. Alterations of Adrenal Function
Disorders of the adrenal
cortex: HYPERCORTISOLISM
– Cushing disease
• Excessive ANTERIOR
PITUITARY secretion
of ACTH
– Cushing syndrome
• Excessive level of
cortisol, regardless of
cause
52. Hypercortisolism: Etiology and Pathogenesis
• PRIMARY adrenocortical hyperfunction due to
disease of the adrenal cortex (adrenal adenoma)
• SECONDARY disease caused by hyperfunction of the
anterior pituitary ACTH-secreting cells
• TERTIARY disease caused by hypothalamic
dysfunction or injury
• EXOGENOUS STEROID use is the most common cause
of Cushing syndrome in the United States
53. Causes of ACTH
Cushing’s Syndrome
Most common cause
54. Cushing’s Syndrome
Redistribution of adipose:
Truncal obesity, moon face, buffalo hump
Protein wasting: limb muscles
Loss of collagen: thin skin, striae, bruising
56. Cushing Syndrome: Clinical Manifestations
Clinical manifestations:
• Round face with flushed cheeks, “moon face”
• Weight gain with excess total body fat, particularly in the
abdomen
• Cervical fat pad, capillary friability, thin skin with formation of
purple striae and ecchymosis over the abdomen, arms and
thighs
• Decreased muscle mass, muscle weakness
• Glucose intolerance, hyperglycemia
• Hypertension
• Demineralization of bone (osteoporosis)
• Increased androgen production causing excessive hair
production, acne, menstrual irregularities
• Emotional changes
57. Characteristic physical features of individuals
with Cushing syndrome include:
A. weight loss and muscle wasting.
B. truncal obesity and thin skin.
C. pallor and swollen tongue.
D. depigmented skin and eyelid lag.
59. ACTH measurement
Primary = low ACTH
Secondary = high ACTH
Urinary free cortisol levels
Dexamethasone suppression
test
60. Cushing Syndrome: Treatment
Treatment is based on etiology
• Exogenous dose reduction
• Pituitary adenomas are treated surgically with
transsphenoidal hypophysectomy, laser ablation, or
radiation
• Adrenal tumor is treated with unilateral
adrenalectomy
• Chemotherapeutic agents block cortisol production
61. Hyperaldosteronism:
• Primary (Conn syndrome)—usually due to
aldosterone-secreting tumors
• Secondary—typically associated with poor kidney
perfusion that stimulates the renin-angiotensin-
aldosterone cascade (heart failure, reduced kidney
perfusion, liver cirrhosis)
62. Hyperaldosteronism:
• Aldosterone facilitates salt and water retention by
the kidney with resultant potassium excretion
• Typically low potassium level
• Treatment includes spironolactone to increase
sodium excretion and potassium retention
• Sodium restriction and potassium replacement may
also be necessary
64. Pheochromocytoma
Etiology and Pathogenesis
Adrenal medulla hyperfunction
• Caused by tumors derived from the chromaffin cells
of the adrenal medulla
– Pheochromocytomas
• Secrete catecholamines on a continuous or episodic
basis
66. Pheochromocytoma: Diagnosis and Treatment
• Diagnosed with abdominal CT/MRI
• Treatment includes sympathetic blocking
medications to manage blood pressure and surgical
removal of the tumor
• If surgery is contraindicated, medication to block
catecholamine production is possible but surgery is
the only curative therapy
68. Parathyroid Gland
What does PTH do?
• Increases serum calcium & decrease serum phosphate
1. Increase bone reabsorption of calcium
2. Increase kidney reabsorption of calcium
3. Decrease kidney reabsorption of phosphate
4. Increase Vitamin D production in kidney
Parathyroid glands
located at the upper
and lower poles of
the thyroid
72. Regulation of Blood Calcium
PTH Calcitonin
• Serum calcium levels provide the • Calcitonin produced by thyroid
feedback to regulate parathyroid parafollicular cells also
hormone (PTH) secretion influences the processing of
• Decrease in calcium causes PTH calcium by bone cells
release
• Calcitonin controls calcium
• Elevated calcium levels lead to
suppression of PTH secretion content of blood by increasing
bone formation by osteoblasts
• PTH acts on bones, intestine, and and inhibiting bone
renal tubules to increase calcium
levels breakdown by osteoclasts
• In bone, PTH increases osteoclastic • Calcitonin decreases blood
activity calcium levels and promotes
• PTH increases renal calcium conservation of hard bone
reabsorption matrix
73. Parathyroid Disorders
Hyperparathyroidism: PTH, Ca+2, Phosphorous
(1) Primary hyperparathyroidism:
• PTH, Ca+2, Phosphorous
• Causes demineralization, extensive resorption
• Hypercalcemia mostly affect the nervous system and kidney
(2) Secondary hyperparathyroidism: secondary to conditions
that cause chronic hypercalcemia of nonparathyroid cause:
major causes:
• Vitamin D-metabolite deficiencies
• High phosphorus load
75. Hyperparathyroidism
Clinical manifestations
• Kidney stones
• Bone demineralization (osteoporosis)
• Polyuria and dehydration
• Anorexia, nausea, vomiting, constipation
• Bradycardia, heart block, and cardiac arrest
76. Hyperparathyroidism
Treatment
• Surgical removal of parathyroid gland
• Medical management includes hydration and ambulation to
maintain bone density
• For hypercalcemic crisis, rapid volume expansion with 0.9%
NS to treat dehydration and improve glomerular filtration
rate; diuretics to increase calcium excretion by the kidneys
77. A problem associated with chronic
hyperparathyroidism is:
A. seizure disorder.
B. vitamin D malabsorption.
C. hyponatremia.
D. osteoporosis and pathologic fractures.
78. Alterations of Parathyroid Function:
HYPOPARATHYROIDISM
– Abnormally low PTH
levels
– Usually caused by
parathyroid damage in
thyroid surgery
79. Parathyroid Disorders
Hypoparathyroidism: PTH, Ca+2, Phosphorous
(1) Primary hypoparathyroidism:
a) Idiopathic hypoparathyroidism
* hormone-deficient hypoparathyroidism
* PTH
b) Pseudohypoparathyroidism
* hormone-sufficient, receptor-deficient hypoparathyroidism
* PTH
(2) Secondary hypoparathyroidism: result from other disorders.
80. HYPOPARATHYROIDISM
Etiology
• Parathyroid or thyroid surgery or surgery in the area of these
glands; may be temporary or permanent
• Permanent hypothyroidism can develop after thyroidectomy
due to damage to parathyroid gland blood supply, postsurgical
swelling, or fibrosis
• Congenital lack of parathyroid tissue and idiopathic
hypoparathyroidism are causes of hypoparathyroidism in
children and infants
• Autoimmune processes may target and damage the
parathyroid glands
81. What happens to serum calcium?
Causes lowered threshold for nerve and muscle excitation
Clinical manifestations
• Circumoral numbness,
paresthesias of the distal
extremities, muscle cramps,
fatigue, hyperirritability,
anxiety, depression, ECG
changes, increases in
intracranial pressure
• Severe symptoms include
carpopedal spasm,
laryngospasm, and seizures
82. Hypoparathyroidism
Treatment
• Acute hypocalcemic crisis (tetany, laryngospasm, and
convulsions)—parenteral calcium administration and
calcitriol, an activated form of vitamin D
• Long-term treatment: oral calcium supplement with vitamin D
84. Antidiuretic Hormone
• ADH (vasopressin) secreted by the posterior pituitary
gland in response to changes in blood osmolality
• ADH acts directly on the renal collecting ducts and
distal tubules, increasing membrane permeability to
and reabsorption of water
The single most important
effect of antidiuretic hormone
is to conserve body water by
reducing the loss of water in
urine
85. DIABETES INSIPIDUS: Antidiuretic Hormone
Disorders:
• Etiology and pathogenesis
– Disorder of INSUFFICIENT
ADH activity resulting in excessive
loss of water in urine
– DAMAGE to ADH-producing cells
in the hypothalamus can result
from:
• Traumatic brain injury
• Intracranial tumors
• Neurosurgical procedures
– Some pharmacologic agents can
lead to abnormalities in ADH
secretion
86. DIABETES INSIPIDUS: Antidiuretic Hormone
Disorders
• Central diabetes insipidus is due to the inability to
produce and release ADH from the pituitary gland
• Nephrogenic diabetes insipidus results from the
INABILITY of the kidneys to respond to ADH due to
chronic renal disease, serum electrolyte
abnormalities, or drugs
87. SIADH: Antidiuretic Hormone Disorders
Syndrome of Inappropriate
Antidiuretic
Hormone (SIADH)
Etiology
• EXCESSIVE ADH from ectopic
production due to several types of
tumors, notably primary lung
malignancies
• Pulmonary tuberculosis
• Drug-induced ADH secretion can occur
89. Clinical Manifestations
Diabetes Insipidus SIADH
• Polyuria, polydipsia • Hyponatremia
• Low urine specific gravity • High urine osmolality
• Hypernatremia due to water • Low serum osmolality
• Cell swelling
deficit
• Weakness, muscle
• Dry mucous membranes, poor
cramps, postural BP
skin turgor, decreased saliva
changes, poor skin
and sweat production turgor, fatigue, anorexia, lethargy
• Disorientation, lethargy, seizur • Confusion, seizures, coma
es
90. Treatment
Diabetes Insipidus SIADH
• Daily replacement of ADH • Free water restriction
with desmopressin (DDAVP) • If severe symptoms, IV
• Free access to fluids administration of saline with
diuretics is used
• Home testing of urine
• Hyponatremia should be
specific gravity
corrected slowly to avoid rapid
changes in brain cell volume
91. The most common cause of elevated levels
of antidiuretic hormone (ADH) secretion
is:
A. autoimmune disease.
B. cancer.
C. pregnancy.
D. heart failure.
92. A 54-year-old patient with pulmonary
tuberculosis (lung infection) is evaluated for
syndrome of inappropriate ADH secretion
(SIADH). Which of the following electrolyte
imbalances would be expected in this patient?
A. Hyponatremia
B. Hyperkalemia
C. Hypernatremia
D. Hypokalemia
