Growing up too fast

Dr S.Agalou, Dr M.Wheeler

St Thomas’ Hospital
Patient’s details
• Sex: Male
• DOB: 01/05/1965

1971
• First GP referral with increased height for age.

• Referral to Guy’s Hospital.

– Skull X-ray. (Normal)
– Oral Glucose Tolerance Test.

• No treatment was administered.

Patient’s history
1981
• Referral to Guy’s Hospital
• Investigation for increased height for age
– 6’6” height
– Gross coarsening of features
– Prognathism
– Severe acne and sweating.

– Tests showed elevated growth hormone

– Diagnosis: Gigantism, still no treatment.

Patient’s growth chart
Patient’s characteristics
11 years 14 years 17 years
Patient’s history
1982
• Referral to St Thomas’ Hospital.
– Skull X-Ray (no malignancies, but possible growth abnormality)
– OGTT (no suppression of growth hormone)
• Diagnosis: Acromegaly with gigantism
35

30

25

20 GH (mg/L)

15

10

5
Glucose (mmol/L)
0
-15 0 15 30 45 60 75 90 105 120 135 150 165 180 195 210 225 240 255 270 285 300

Time (min)
Patient’s history
1982
• Referral to St Thomas’ Hospital.
– Skull X-Ray (no malignancies, but possible growth abnormality)
– OGTT (no suppression of growth hormone)
• Diagnosis: Acromegaly with gigantism
35

30

25

20 GH (mg/L)

15 GH on br (mg/L)

10
Glucose on br
(mmol/L)
5
Glucose (mmol/L)
0
-15 0 15 30 45 60 75 90 105 120 135 150 165 180 195 210 225 240 255 270 285 300
Time (min)
Patient’s history
1983

• Referral to Skin Clinic with severe acne.

– Prescribed Minocin 100 mg b.d., Betadine skin cleanser
– UV therapy

• OGTT on the basis of features and growth chart

– Growth hormone still elevated -GH :20-30mg/L (<0.2mg/L)
Hypophysectomy

•Operation: Transsphenoidal Hypophysectomy

•Findings: Large dural sinus with an adenoma removed by suction despite great
fundal sinus bleeding

•Results upon discharge

•Insulin Tolerance Test (marginally abnormal)
•Cortisol secretion rate: 64mmol/day (22-82mmol/day)
•OGTT
•Normal glucose tolerance: 4mmol/L (2.8-6.0 mmol/L)
•GH high :16-17mg/L

•Further Treatment: X-Ray Therapy (3600 cGy in 12 treatments over 28 days)

Patient’s history
Sinusitis,
skin problems,
10 depression 68

9 66
8 Upper
64 limit of
7 normal
62 IGF-1
GH (mU/L)

6
Cortisol 140nmol/L

IGF-1 (nmol/L)
5 Prolactin 370mU/L 60
Two tachycardic
episodes
4
58
3
56
2
Normal 54
range of 1
GH
0 52
Patient’s present

• Clinically stable

• Has a check up every two years

• Father of two children (4 and 11 years old)

Gigantism and Acromegaly

Definition

• Gigantism
– excessive linear growth
– occurs with growth hormone (GH) excess when epiphyseal growth
plates are open during childhood.

• Acromegaly
– indicates the disorder of GH excess in adulthood.
Pathophysiology

•Most incidents of gigantism are caused by GH-secreting pituitary

adenomas or hyperplasia.

•Gigantism occasionally may present as a feature of other conditions,

such as:
–Multiple endocrine neoplasia type I
–McCune-Albright syndrome
–Neurofibromatosis
–Tuberous sclerosis
–Carney complex
Gigantism and Acromegaly

Morbidity/Mortality
• Rates for gigantism are unknown.

• In acromegaly the mortality rate is 2-3 x general population.

• Cardiovascular and respiratory complications.

• Robert Wadlow, the “Alton Giant,”

– 8 feet 11 inches

• Andre Rousimoff, "Andre the Giant,"

– 6 feet 3 inches at 12 years

– 7 feet 4 inches by adulthood.

Gigantism and Acromegaly

• Andre Rousimoff (note the acromegalic

features of his hand)
• Robert Wadlow, the tallest that ever
lived.
Gigantism and Acromegaly

Physical Characteristics
• Progressive cosmetic disfigurement and systemic organ manifestations.
• Physical manifestations include the following:
– Tall stature
– Mild-to-moderate obesity (common)
– Macrocephaly (may precede linear growth)
– Soft-tissue hypertrophy
– Exaggerated growth of the hands and feet with thick fingers and toes
– Coarse facial features
– Frontal bossing
– Prognathism
– Hyperhidrosis
– Osteoarthritis (a late feature of GH excess)
– Peripheral neuropathies (ie, carpel tunnel syndrome)
– Cardiovascular disease
– Frequently associated endocrinopathies including hypogonadism, diabetes and/or decreased
glucose tolerance, and hyperprolactinemia
Gigantism and Acromegaly

Biochemical Tests

• Serum IGF-1 concentrations

– Sensitive screening test for acromegaly.
– Elevated IGF-1 in a patient whose symptoms prompt appropriate clinical
suspicion almost always indicates GH excess.

• Serum insulin like growth factor-binding protein-3

– IGFBP-3 also may help diagnose GH excess.

• Serum GH
– Inability to suppress serum GH during an OGTT is the criterion standard for
diagnosing GH excess.
– Failure to suppress serum GH < 5 mg/L after a 1.75 g/kg oral glucose challenge
is diagnostic.
Gigantism and Acromegaly

Imaging Tests
• MRI
– to confirm the presence of a pituitary adenoma
– Rarely, a pituitary mass may not be identified
– ? occult pituitary microadenoma or an ectopic tumor.

• CT
– Acceptable imaging study if MRI is unavailable.

• Chest / abdominal imaging

– may identify the rare ectopic GH-secreting or GHRH-secreting tumor.

Other Tests
• Paradoxic rise in GH after iv thyrotropin-releasing hormone (TRH).
• Circulating GHRH may confirm peripheral ectopic GHRH secretion in the presence of
an ectopic tumor.
Gigantism and Acromegaly

Medical Care:
• Somatostatin analogs.

• Dopamine agonists (eg, bromocriptine) .

• Novel hepatic GH receptor antagonist Pegvisomant

– effective suppression of GH / IGF-1 in patients with acromegaly.

Gigantism and Acromegaly

Surgical Care:
• Transsphenoidal surgery

• The primary goal of treatment is to normalize GH levels.

• If surgery does not normalize GH secretion

– Pituitary radiation

– Medical therapy.
Acknowledgements

Special thanks to: Dr Mike Wheeler,

Miss Sophie Barnes
Miss Fiona Carragher

For their help and guidance during the preparation of this presentation.