The document discusses dwarfism, gigantism, and acromegaly which are conditions caused by abnormal growth hormone levels from the pituitary gland. Dwarfism is caused by a growth hormone deficiency and results in short stature. Gigantism occurs in children and is caused by excess growth hormone before growth plate closure, leading to abnormally large growth. Acromegaly occurs in adults and has similar causes to gigantism but growth occurs after growth plate closure. The document defines the conditions, describes their pathophysiology and genetic causes, lists clinical features, and discusses diagnostic criteria and treatment options.

1. Dwarfism, Gigantism, and
Acromegaly

3. Objectives
• By the end of this lecture, the students will
be able to:
• Define dwarfism gigantism and acromegaly
• Describe the Pathophysiology of
acromegaly and gigantism
• List the clinical features
• Elaborate the diagnostic criteria
• Discuss the medical management
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4. Which Gland is involved?
• The Pituitary Gland is a
pea- sized gland located
at the base of the skull.
• This gland secretes many
hormones and is referred
to as the “Master Gland”
because it controls
hormone functions all over
the body.
The Pituitary Gland
The GH gene is located on chromosome
17 (Chen et al., 1989).
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5. What is growth hormone
• A hormone that stimulates growth in animal or plant
cells, esp. (in animals) a hormone secreted by the
pituitary gland.
• Growth hormone (GH) is a protein-based peptide
hormone. It stimulates growth, cell reproduction and
regeneration in humans and other animals. Growth
hormone is a 191-amino acid, single-chain
polypeptide that is synthesized, stored, and secreted
by the somatotroph cells within the lateral wings of
the anterior pituitary gland.
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6. Major functions of growth hormone
• Stimulate growth and cell production in humans.
• It is synthesized, stored, and secreted by the
somatotroph cells within pituitary gland.
• Human growth hormone is used clinically to treat
children's growth disorders and adult growth
hormone issues.
• Recently human growth hormones (HGH) have
become used against aging and weight loss.
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8. • The Anterior Pituitary Gland produces human growth hormone (hGH or
GH), also known as somatotropin.
• GH binds to receptors on liver cells and they release insulin- like growth
factor- 1 (IGF-1).
• This hormone causes body cells to grow and stimulates protein synthesis
within cartilage, bones, and muscle.
• This hormone increases the growth rate of bones and muscles during
childhood.
• GH also has many effects on metabolism
• GH stimulates the rate at which amino acids enter cells and protein
synthesis occurs.
• GH stimulates fat and carbohydrate metabolism.
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9. Negative Feedback loop of the
Growth Hormone
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10. Amount of Growth Hormone
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11. Dwarfism
• Hypo secretion of the GH
• Condition caused by
insufficient secretion of
growth hormone during
childhood.
• Short limb structure
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Shortest Man to ever Live: Gul
Mohammed: 22.5 inches tall,
lived to age 29

12. Cont…
12
• Caused by deficiency of
Pituitary Gland
– Limited production of
GH, called
somatotrophin
• Growth failure, distorted
facial appearance, delayed
bone age and many organ
problems
Shortest Woman to ever
Live: Pauline Musters: 23
inches tall, lived to age 19

13. Genetics
• Diastrophic dysplasia and usually spondyloepiphyseal dysplasias are
inherited in a recessive manner. This means a child must receive two
copies of the mutated gene -- one from the mother, one from the father --
to be affected.
• Achondroplasia, on the other hand, is inherited in a dominant manner.
That means a child needs only one copy of the mutated gene to have that
form of skeletal dysplasia. There is a 25% chance that a child born to a
couple in which both members have achondroplasia will be of normal
height. But there is also a 25% chance the child will inherit both dwarfism
genes, a condition known as double-dominant syndrome. This is a fatal
condition that usually results in miscarriage.
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17. Young female dwarf standing next to
a boy of normal stature
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18. Classification of Dwarfism
1. Achondroplasia. Achondroplasia is a form of short-limbed dwarfism. The
word achondroplasia literally means "without cartilage formation
The most common form of dwarfism, achondroplasia occurs in about one out
of 26,000 to 40,000 babies and is evident at birth. People with
achondroplasia have a relatively long trunk and shortened upper parts of
their arms and legs. Other features of achondroplasia include:
• A large head with a prominent forehead
• A flattened bridge of the nose
• Protruding jaw
• Crowded and misaligned teeth
• Forward curvature of the lower spine
• Curved legs flat, short, broad feet
Mutations in the FGFR3 gene cause achondroplasia. The FGFR3 gene provides
instructions for making a protein that is involved in the development and
maintenance of bone and brain tissue. Two specific mutations in the FGFR3
gene are responsible for almost all cases of achondroplasia.
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19. Cont…
2. Spondyloepiphyseal dysplasias (SED). A less common form
of dwarfism, SED affects approximately one in 95,000 babies.
Spondyloepiphyseal dysplasia refers to a group of conditions
characterized by a shortened trunk, which may not become
apparent until a child is between 5 and 10 years old. Other
features can include:
• Club feet
• Cleft palate
• Severe osteoarthritis in the hips
• Weak hands and feet
• Barrel-chested appearance
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20. 3. Diastrophic dysplasia. An autosomal recessive dysplasia which
affects cartilage and bone development. ("Diastrophism" is a general
word referring to a twisting. Diastrophic dysplasia is due to
mutations in the SLC26A2 gene
A rare form of dwarfism, diastrophic dysplasia occurs in about one in
100,000 births. People who have it tend to have shortened forearms
and calves (this is known as shortening of the middle of the bone
(mesomelic) shortening).
• Other signs can include
• Deformed hands and feet
• Limited range of motion
• Cleft palate
• Ears with a cauliflower appearance
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21. Diagnosis
• X rays of the long bones
• Blood tests for growth hormones
• MRI of the head
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Treatments for Dwarfism
• Daily injections of
Human Growth
Hormone (HGH)

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Gigantism
• "Pituitary gigantism" and
Hyper secretion of the GH
• Bone growth in an excess
amount
• Can result in “hoarseness,
sleep apnea, joint pain,
cardiovascular disease,
hypertension, insulin
resistance, visual impairment
and severe headaches”
Tallest Man to ever Live:
Robert Wadlow: 8’11.1”,
lived to age 22
Gene on the X chromosome,
GPR101, which was over
expressed 1000-fold more than
normal

24. Cont…
Overproduction of growth hormone causes excessive
growth. In children, the condition is called gigantism.
In adults, it is called acromegaly.
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25. • Gigantism is an abnormally large growth
due to excess growth hormone during
childhood, before growth plates close.
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Cont…

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27. Clinical features
Excessive growth
The child is large for their age
Delayed puberty
Double vision or difficulty with peripheral vision
Headaches
Increased sweating
Large hands and feet
Thickening of facial features
Weakness
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28. Investigations
• CT scan
• MRI
• GH raised level
• IGF-1 raised level
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29. Treatment
Surgery
 Transsphenoidal surgery to remove the
pituitary adenoma
Radiation therapy
Drug therapy
 Bromocriptine
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30. Acromegaly
Acromegaly is a hormonal disorder that results
when the pituitary gland produces excess growth
hormone (GH)
After puberty
The name acromegaly comes from the Greek
words for "extremities" and "enlargement“.

31. Cont...
• Overproduction of growth hormone causes
excessive growth. In children, the condition is
called gigantism. In adults, it is called
acromegaly.
Epidemiology of Acromegaly:
• Acromegaly is a relatively uncommon disease,
and studies estimate that its prevalence is
between 50 to 70 cases per million people
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32. Pathophysiology of Acromegaly
• Characterized by growth hormone (GH) excess
• Typically caused by a GH-secreting pituitary
adenoma
• Uncontrolled tumor GH production causes
elevated serum IGF-I
• Increased GH and IGF-I levels cause the signs
and symptoms of acromegaly.
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33. Causes
• Caused by prolonged overproduction of GH by
the pituitary gland.
• Pituitary tumors
– Pituitary adenoma
• Ectopic production of GH by other tumors (e.g.,
cancers of the pancreas or lung)
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34. Sign and Symptoms
• Growth hormone stimulates the growth of bones, muscles,
and many internal organs
• Swelling of the hands and feet
• Facial features become coarse as bones grow
• Protruding jaw
• Voice deepening (Cartilage in the voice box (larynx) may
thicken)
• Enlarged lip, nose, and tongue
• Degenerative arthritis
• Thickened ribs (creating a barrel chest)
• Joint pain
• Enlarged heart
• Offensive body odor
• Galactorrhea
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36. Cont…
• Enlargement of other organs
• Snoring
• Fatigue and weakness
• Headaches
• Loss of vision
• Irregular menstrual cycles in women
• Increased incidence of obstructive sleep apnea
• Frontal bossing
• Thickening of the nose
• Macroglossia
• Prognathism
• Women can have mild hirsutism.
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38. Supra orbital ridge
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39. Investigations
• X-ray of the skull
– Show thickening of the bones and enlargement
of the nasal sinuses.
• X-rays of the hands
– Show thickening of the bones under the
fingertips and swelling of the tissue around the
bones.
• Blood sugar
– Blood sugar levels high
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40. Treatment
Surgery
 Transsphenoidal surgery to remove the
pituitary adenoma
Radiation therapy
Drug therapy
 Bromocriptine
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41. References
• American Association of Clinical Endocrinologists Medical guidelines for clinical
practice for the diagnosis and treatment of acromegaly. Endocrine Practice.
2004;10:213-225.
• Buehler BR, Henzen CM, de Zulueta MT, Ross RA. Acromegaly and colorectal cancer. J
Applied Res. 2004;4:257-260.
• Melmed S, Kleinberg D. Anterior pituitary. In: Larsen PR, Kronenberg HM, Melmed S,
Polonsky KS, eds. Williams Textbook of Endocrinology. 10th ed. Philadelphia Pa.: WB
Saunders Company; 2003:177-260.
• Molitch ME. Clinical manifestations of acromegaly. Endocrinol & Metab Clin North
Am. 1992;21:597-614.
• Melmed S, Casanueva F, Cavagnini F, Chanson P, et al. Consensus statement: Medical
management of acromegaly. Eur J Endocrinol. 2005;153:737-740.
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