Endocrine & Metabolic Disorders

Imran Yousafzai
Lecturer, KMU

Imran Yousafzai
 Hypothalamic Hormones Regulating
Hormones
• GH-releasing hormone (GHRH)
• Somatostatin
• Somatomedin----IGF-1

Imran Yousafzai
 Physiologic Effects of Growth Hormone

• Direct effects are the result of growth hormone binding its receptor on
target cells. Fat cells (adipocytes), for example, have growth hormone
receptors, and growth hormone stimulates them to break down
triglyceride and suppresses their ability to take up and accumulate
circulating lipids.

• Indirect effects are mediated primarily by a

Imran Yousafzai
Imran Yousafzai
 Growth Hormone:
• Necessary for linear bone growth in children
• Stimulates cells to increase in size and divide more
rapidly
• Enhances protein synthesis.
• Increases fatty acid mobilization and the rate at
which cells use fatty acids
• anti-insulin effect

Imran Yousafzai
Imran Yousafzai
 Abnormalities in GH Secretion

Hypersecretion of GH
• Gigantism
• Acromegaly

Hyposecretion of GH
• Dwarfism

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 Growth Hormone in Children
• GH deficiency
– Interferes with linear bone growth
– Results in short stature or dwarfism
– Epiphyseal plates close before the normal height
is reached.
• GH excess
– Results in increased linear bone growth
– Gigantism

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 Effects of Growth Hormone Excess in
Adults:
• Overgrowth of the cartilaginous parts of the
skeleton
• Enlargement of the heart and other organs of
the body
• Metabolic disturbances resulting in altered fat
metabolism and impaired glucose tolerance

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Dwarfism:

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 Dwarfism or Short stature :
• Short stature is a condition in which the
attained height is well below the fifth
percentile or linear growth is below normal
for age and sex.

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 Pathology of Hyporsecretion of GH
• Several pathologic processes may result in pituitary
insufficiency:-
• Pituitary tumor that destroys normal pituitary cells.
• Vascular thrombosis that leads to necrosis of the
normal pituitary gland.
• Infiltrative granulomatous disease that destroy the
pituitary.
• Idiopathic or possible autoimmune destruction of
pituitary cells.

Imran Yousafzai
 Causes of Short Stature:
• Variants of normal
- Genetic short stature
- Constitutional short stature
• Chronic illness and malnutrition
- Renal failure
- Nutritional deprivation
- Malabsorption syndrome
• Functional endocrine disorders
- Psychological dwarfism
• Chromosomal disorders
- Turner’s syndrome
• Skeletal abnormalities
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 Causes cont…
Endocrine disorders:
• Primary GH deficiency
- Idiopathic GH deficiency
- Pituitary agenesis (Panhypopituitarisim)
• Secondary GH deficiency
- Hypothalamic- pituitary tumor
- Head injuries, Brain infection &
hydrocephalus
• Biologically inactive GH production
• Hereditary defect in IGF receptor
• Hypothyroidism
• Diabetes mellitus in poor control
• Glucocorticoid excess, cushing syndrome

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 Gigantism:
• Gigantism is an excessive secretion of
growth hormone during childhood before the
closure of the bone growth plates, which
causes overgrowth of the long bones and very
tall stature.
• Usually resulting from a tumor of
somatotropes.
• Genetic & chromosomal disorders

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Robert Wadlow at age thirteen, standing 7 feet, 4
inches tall. He suffered from Hyper Pituitarism.
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 Acromegaly:
• This condition resulting when GH excess occur
in adulthood or after the epiphyses of long
bones have fused.
• disorder has insidious onset.
• The mean age at the time of diagnosis is about
40 for men and 45 for women.

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 Causes of Acromegaly:

• Most common cause (95%)

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Imran Yousafzai
 Clinical Manifestation:
Features that result from high level of hGH or
expanding tumor include:
• Soft tissue swelling of the hands and feet
• Lower jaw protrusion
• Broad and bulbous nose
• Enlarging hands
• Enlarging feet
• Arthritis and carpal tunnel syndrome
• Teeth spacing increase
• Macroglossia [enlarged tongue]
• Heart failure
• Kidney failure Imran Yousafzai
Imran Yousafzai
 Other symptoms of acromegaly include

• joint aches
• thick, coarse, oily skin
• skin tags
• enlarged lips, nose, and tongue
• deepening of the voice due to enlarged sinuses and
vocal cords
• sleep apnea—breaks in breathing during sleep due to
obstruction of the airway
• excessive sweating and skin odor
• fatigue and weakness
• headaches

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• loss of vision in the outer visual fields
• secondary hypothyroidism hypogonadism & adrenal
insufficiency.
• Bitemporal Headache
• Impaired glucose tolerance lead to Diabetes mellitus
• Hypertension
• Cardiomegaly
• Increased palmer sweating
• Increased sebum production over the face
(seborrhea)
• Cartilaginous structure of larynx and respiratory tract
also enlarged resulting deepening of voice and
bronchitis
• Kyphosis or hunchback

Imran Yousafzai
Imran Yousafzai
 Diagnosis
• If acromegaly is suspected, medical imaging and medical
laboratory investigations are generally used together to confirm
or rule out the presence of this condition.
• Hormonal
• IGF1 provides the most sensitive and useful lab test for the
diagnosis of acromegaly.
• GH levels taken 2 hours after a 75 or 100 gram glucose tolerance
test : GH levels are suppressed below 1 μg/L in normal people,
and levels higher than this cutoff are confirmatory of acromegaly.

• Radiological
• An MRI of the brain focussing on the sella turcica for clear
demarcation of the pituitary and the hypothalamus and the
location of the tumor.

Imran Yousafzai
 Treatment Goals for Acromegaly:
• Normalization of the GH to prevent or reverse
progression of the discorder
• Normalization of IGF-1 levels to age- and sex-
matched control levels
• Removal or reduction of the tumor mass
• Relieving the central pressure effects
• Improvement of adverse clinical features
• Normalization of the mortality rate

Imran Yousafzai