THEORY
FUNCTIONS OF PITUITARY HORMONES
Hormones secreted from the pituitary gland help control the following body processes:
1. Growth
2. Blood pressure
3. Some aspects of pregnancy and childbirth including stimulation of uterine contractions during childbirth
4. Breast milk production
5. Sex organ functions in both males and females
6. Thyroid gland function
7. The conversion of food into energy (metabolism)
8. Water and osmolarity regulation in the body
9. Water balance via the control of reabsorption of water by the kidneys
10. Temperature regulation
11. Pain relief
DISEASES INVOLVING THE PITUITARY GLAND
Some of the diseases involving the pituitary gland are:
1. Central diabetes insipidus caused by a deficiency of vasopressin.
2. Gigantism and acromegaly caused by an excess of growth hormone. --- PBL Ph2 Yr2 MD Wk1 Topic1
3. Hypothyroidism caused by a deficiency of thyroid-stimulating hormone.
4. Hyperpituitarism, the increased (hyper) secretion of one or more of the hormones normally produced by the pituitary gland.
5. Hypopituitarism, the decreased (hypo) secretion of one or more of the hormones normally produced by the pituitary gland.
6. Panhypopituitarism a decreased secretion of most of the pituitary hormones.
7. Pituitary tumours.
8. Pituitary adenomas, noncancerous tumors that occur in the pituitary gland.
GROWTH HORMONE (GH)
GH is growth hormone, or somatotropin
GH is a single polypeptide chain containing 191 amino acids.
GH has structural similarity with prolactin and human placental lactogen.
GH is synthesised by acidophils (somatotropic cells) of anterior pituitary.
GH has a circadian rhythm;
- plasma concentration of GH is less than 2 ng/ml during day time,
- with secretory peak appearing 3 hr after meals.
- maximum level of GH is seen during deep sleep;
- this peak is required for anabolic and repair process.
GH secretion is regulated by the balance between GHRH and GHIH (somatostatin).
The regulation of secretion is predominantly inhibitory.
Hypoglycemia stimulates GH secretion.
Hyperglycemia suppresses GH secretion.
The metabolic effect of GH is partly mediated by somatomedin.
Somatomedin is also known as insulin-like growth factor-1 (IGF-1).
The growth of long bones is stimulated by IGF-1.
IGF-1 level is almost always raised in acromegaly.
A single plasma level of IGF-1 reflects mean 24-hour GH level and is useful in diagnosis.
GH increases the uptake of amino acids by cells.
GH enhances protein synthesis, and produces positive nitrogen balance.
The anti-insulin effect of GH causes lipolysis and hyperglycemia.
The overall effect of GH is to stimulate growth of soft tissues, cartilage and bone.
GH is anabolic.
Excess secretion by GH secreting tumour, leads to
- gigantism in children
- acromegaly in adults.
Deficiency of GH secretion in early childhood results in pituitary dwarfism.
Dwarfism may also result from congenital deficiency of GH due to end organ resistance.
Dwarfism is treated by giving GH produced by recombinant technology.
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PRACTICAL
SERUM GH
The samples are collected during sleep and also during waking hours to assess the circadian rhythm.
Random plasma GH is elevated.
GH SUPPRESSION TEST (glucose suppression test)
Basis of the GH suppression test:
Dynamic tests like stimulation of secretion by insulin induced hypoglycemia and inhibition by hyperglycemia are undertaken to arrive at a diagnosis.
Procedure:
Measure plasma glucose and GH during a standard OGTT.
Interpretation:
(i) In normal person:
Normally in healthy individuals, oral administration of 100 g glucose causes a reduction of the GH level to <5 br="" ml.="" ng=""> (ii) In acromegaly:
Acromegalics (with GH excess) fail to suppress GH level. In acromegaly, the GH levels may decrease, increase or show no change. However, they do not decrease to less than 5 ng/ml and this lack of response establishes the diagnosis. High GH levels are sustained in acromegalics.
(iii) Patient:
In this patient, the GH level is not suppressed (ie sustained) and remained high during the test, Therefore, patient suffers from acromegaly.
BLOOD GLUCOSE
Check if patient is diabetic.
Check for hyperglycaemia.
RBS is high (>11.1 mmol/L) - patient has hyperglycaemia most likely due to diabetes mellitus as patient is symptomatic with lethargy, polyuria and polydipsia.
OGTT
Oral glucose tolerance test (OGTT). Administer 100 g glucose solution (dissolve in a glass of water).
HBA1C
Glycosylated haemoglobin (HbA1c) provides an index of the average blood glucose concentration over the last 6 weeks (lifespan of Hb molecules).
URINALYSIS (urine dipstick test)
Test urine for sugar, ketones and protein.
Urine sugar - check for glycosuria (in polyuria and polydipsia)
Urine ketone - check for ketonuria which occurs in diabetic ketonuria
Urine protein - check for proteinuria (renal involvement in diabetes)
Urine sugar is positive - glycosuria is not diagnostic of diabetes but indicates the need for further investigation.
Urine protein is negative - indicates there is no renal involvement as diabetic nephropathy.
Urine ketone is negative - indicates patient does not have ketoacidosis.
UREA, CREATININE and ELECTROLYTES (renal profile)
Serum urea, creatinine and electrolytes - to check for renal status as patient has polyuria.
Serum sodium and potassium are normal - indicate that patient does not have hypoadrenalism, hypothyroidism (hyponatraemia), or diabetes insipidus (hypernatraemia).
Serum urea - decreased serum urea in acromegaly.
Serum creatinine - increased serum creatitine in gigantism and acromegaly.
CALCIUM
Serum calcium - high with hypercalciuria in acromegaly. Matches with renal stone formation.
Hypercalciuria and hyperphosphaturia are observed in acromegalic patients. It is well known that acromegaly is associated with the disturbances of Ca and PO4 metabolism, and consequently with an increased risk of Ca stones.
ENZYMES
Heart muscle enzyme:
Creatinine kinase (CK) - elevated in myopathy
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Abnormal findings
ENT / ORL-HNS:
Coarse facies - Increased level of GH causes thickening of the soft tissues, overgrowth of the malar, frontal and facial bones combined with prognathism to produce the coarse facial features called acromegalic facies.
Facial and infraorbital puffiness - ?
Broad nose
Big ear
Dentistry:
Widening of the teeth / interdental separation
Prognathism - widely spaced teeth
Speech Pathology:
Large tongue
Thick lips
Deep voice
Medicine:
Hypertension - investigate further
CXR
ECG
Echocardiogram
Urinalysis
Fasting blood for lipids and glucose
Serum urea, creatinine and electrolytes
Cardiology:
Heart failure
Proximal myopathy
Ophthalmology:
Visual field examination
Visual field testing by Goldmann perimetry - it can assess any visual field defect as upper temporal quarantonopias and bitemporal hemianopias. Perimetry can also assess the tujour size.
Papilloedema - increased intracranial pressure from the pituitary tumour causes edema of the optic disc.
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Endocrinology
Pituitary
- anatomy of the pituitary gland
- hormones released by the anterior lobe of pituitary: GH, ACTH, LH, FSH, TSH, aMSH (intermediate lobe), PRL, bLPH
- hormones released by the posterior lobe of pituitary: ADH, oxytocin
- processes involved in the release of these hormones
- biological functions of these hormones
- control mechanisms that affect hormone production, release and function
- types of pituitary tumours
- hyperfunction, hypofunction
Assessment of anterior pituitary reserve or function - as patient may have hypopituitarism:
Basal LH
FSH
Testosterone
ACTH
Cortisol
Free/Total T4
TSH
Triple Stimulation Test
LHRH/GnRH, TRH, insulin tolerance test (ITT) can be done to assess the function of the anterior pituitary. Early LH failure can occur
followed by hypothyroidism and hypoadrenalism.
Hypothyroidism (free/total T4 is low with a low or normal TSH level) must be excluded since this is a cause of hyperprolactinaemia.
Serum prolactin
Mild to moderate hyperprolactinaemia occurs in pituitary tumour.
Pituitary tumour is suspected if patient has papilloedema, indicating increased intracranial pressure from a pituitary tumour.
Serum prolactin - is due to hyperprolactinaemia that can result from a pituitary tumour, which is evident from the CT scan of the brain.
Endocrinology/Medicine:
Galactorrhoea
Edema plus other signs of hypopituitarism
Goitre
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Patient workup:
History
Physical examination
Presenting clinical features
Pathological features
Radiological features
Laboratory investigations
Deduce possible patient problem
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Medicine
Pathophysiology of:
I. Pituitary hypersecretion:
- Gigantism
- Acromegaly - face, hands **
- Prolactin-induced infertility
- Craniopharyngioma
- Cushing's disease
II. Pituitary hyposecretion:
- Pituitary dwarfism
- Panhypopituitarism
- Diabetes insipidus
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Radiology
Imaging studies:
Skull X-ray - enlargement/widening of the pituitary fossa, double flooring, calcification
MRI scan of the pituitary - to rule out suspicion of a pituitary tumour as patient has history of headache and papilloedema.
Lateral X-ray of the heel - assessment of soft tissue thickness by measuring heel pad thickness.
X-ray of hand - Large hands, thickened and bulky with blunt spade-like fingers (similar findings in the toes - spade-like feet)
Large hands and sweaty - The hands enlarge from increased soft tissue growth. Sebaceous activity increases causing excessive sweating.
Increased joint space due to hypertrophy of cartilage, cortical thickening with result in squared appearance of the metacarpals.
Small exostoses in the areas of tendons and ligament insertion and are obvious in the head of the metacarpals.
Tufting of the terminal phalanges producing an "arrow-head" appearance.
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Possible complications:
Cardiovascular problems - CAD, related to HPT and DM
Arthritis - occurs prematurely in spine and weght-bearing joints (hips, knees)
Malignancy - colon cancer is increased.
Arthropathy - disease of the joints
Tight rings - excessive fat
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Treatment and Management
Surgery - vi transphenoid/transfrontal route
Radiotherapy
Medical therapy - using a somatostatin analogue (octreotide) or dopamine agonist (bromocriptine).
Principles of hormone replacement therapy (HRT) in pituitary dysfunction
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Further Reading
Basic and Clinical Endocrinology. Francis S. Greenspan. Acromegaly and gigantism. Clinical findings on page 119.
Steven WJ Lamberts. Non-functioning pituitary tumours and hypopituitarism. Medicine International on Endocrine Diseases. No. 38
Volume 11, 1997, pages 1-4.
JAH Wass. Acromegaly. Medicine International on Endocrine Diseases. No 38 Volume 11, 1997, pages 5-6.
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Videos
http://umm.edu/health/medical/ency/animations/pituitary-gland
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Research & Case Studies
http://www.eje-online.org/content/162/6/1035.full
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Websites
http://www.chronolab.com/point-of-care/index.php?option=com_content&view=article&id=388&Itemid=63
http://www.rnceus.com/renal/renalcreat.html
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