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Chapter 13
Endocrine diseases
These diseases arise as a result of malfunction
of the endocrine glands, structures that secrete
hormones.
The endocrine glands do not have excretory
ducts as do other glands such as the salivary
and sweat glands.
Their secretions are passed directly into veins.
As a result of this mechanism the endocrine
glands are extremely vascular.
The endocrine glands, together with the
hormones they secrete are listed below.
Small foci of endocrine tissue are found in
other organs, e.g. the gastrointestinal tract the
placenta and the respiratory tract.
Only the main endocrine glands will be
discussed in this chapter.
Hormones govern most of the main functions of
the body – metabolism, maintenance of blood
pressure, maintenance of fluid and electrolyte
balance, growth, and sexual development and
differentiation of the body.
When the body is functioning normally there
are feedback mechanisms that control the
amount of hormone secreted so that the body
responds appropriately to the ever changing
stresses placed upon it during every day life.
They also influence the psyche as shown by the
fact that a number of endocrine diseases result
in reversible psychiatric conditions.
Not surprisingly, therefore, many endocrine
diseases produce changes in bodily appearance
and function that can be recognized both by the
patients and their medical attendants.
These changes come on slowly and it is useful
to look at family photographs to appreciate the
changes, and when they first began to appear.
Endocrine glands and the hormones they
secrete:
Pituitary
Anterior lobe
ACTH (adrenocorticotrophic hormone)
GH (growth hormone)
FSH (follicle stimulating hormone)
LH (Leuteinizing hormone)
TSH (thyroid stimulating hormone)
Lactogenic hormone (prolactin)
MSH (melanocyte stimulating hormone)
Posterior lobe
ADH (antidiuretic hormone)
Oxytocin
Thyroid
Thyroxin
Calcitonin
Parathyroid
Parathormone
Pancreas
Islet cells
Insulin
Glucagon
Adrenal
Cortex
Cortisol
Sex hormones
Aldosterone
Medulla
Adrenalin
Noradrenalin
Gonads
Female
Oestrogen
Progesterone
Male
Testosterone
Laboratory tests are done to clarify the
biochemical abnormalities.
Some of the tests in use in 2008 are listed in the
appendix.
2
These test results are for information only.
They are intended for reference and not for
committing to memory.
Imaging techniques are used to make an exact
anatomical diagnosis.
Treatment may be medical,
to counteract the effects of the excessive
hormone secretion,
or therapy to replace the hormone deficiency.
Many of the endocrine diseases are caused by
secretions that come from tumours that develop
in the glands.
These tumours are removed by surgeons, and
the gross and microscopic features of the
tumours are assessed by pathologists.
In general terms the main diseases of the
endocrine glands result from
overproduction or
underproduction
of one or more of the hormones normally
secreted by the glands.
In this chapter clinical and pathological features
of many of these diseases will be illustrated.
Pituitary
The pituitary gland is an organ approximately
10 mms in diameter.
It is connected to the undersurface of the brain,
below the hypothalamus by a pituitary stalk.
The gland itself is housed in a bony aperture
called the pituitary fossa.
1 This is a view looking down into the base of
the skull with the brain removed.
The green arrow indicates the pituitary stalk
that has been cut from the hypothalamus at the
base of the brain when the brain was removed.
It connects to the pituitary gland that can just be
seen in the bony pituitary fossa.
carotid artery and
cranial nerves, 111, 1V, V and VI.
These nerves may be damaged when the
pituitary fossa is expanded by
a tumour of the pituitary gland, or
by an aneurysm of one of the arteries that form
the circle of Willis which surrounds the stalk of
the pituitary.
On its anterior aspect the pituitary lies just
posterior to the optic chiasm.
Enlargement of the pituitary can cause pressure
on the posterior aspect of the chiasm with
symptoms of visual field defects for example,
bitemporal hemianopia.
The blue arrows indicate the two internal
carotid arteries.
The nerves in the hypothalamus react to the
electrical and hormonal activity of the body by
activating the secretion of hormones by the
various cells in the pituitary.
(a) x1
2(a) The pituitary gland is divided into 3 parts
as can be seen in this horizontal section.
Anterior lobe (A)
Posterior lobe or the pars nervosa (P)
Pars intermedia. (black arrow)
The blood supply comes from two different
sources.
The main supply comes from the hypothalamus
to the main mass of the pituitary.
A second supply comes from the connective
tissue that surrounds the pituitary (red arrow).
This supplies the rim of cells on the periphery
of the gland.
Some of the connective tissue can be seen on
the right hand side of the section.
(b) x20
(c) x20 (PAS + Orange G)
The outer sides of the lateral walls of the
pituitary fossa are lined by layers of dura mater
in which pass
cavernous sinus,
2(b) and (c) Three types of cells can be
distinguished in the anterior lobe according to
their affinity for special stains.
3
Chromophobes (white arrow),
Basophils (blue arrow)
Acidophils (red arrow).
These cells are not easy to distinguish in the
H&E stain 2(b).
They are more easily seen in a special stain
called a PAS + Orange G. 2(c).The acidophils
stain a yellow colour with this stain.
The posterior clinoid processes of the pituitary
fossa are clearly seen.
4 Slice of brain showing a large pituitary
tumour. (blue arrows)
Death occurred from haemorrhage into the
tumour. This was a common end result in these
tumours before the availability of modern
imaging techniques and neurosurgery.
(d) x10
2(d) The pars intermedia (black arrow) consists
of fluid filled spaces lined by cuboidal
epithelial cells.
This part of the pituitary arises from the
epithelium of the roof of the mouth.
With the introduction of immunological
staining methods it has become possible to
identify the cell types in the anterior lobe of the
pituitary according to the hormone they secrete
rather than by their staining affinities.
Hyperpituitarism
Cells in the anterior pituitary may produce a
tumour which grows slowly. In so doing it
causes enlargement of the pituitary fossa and
pressure on adjacent brain tissue.
When the tumour reaches a size big enough to
cause symptoms, the enlarged pituitary fossa
can be seen on a lateral X ray of the skull.
(a)
3(a) and (b)
(a) This skull X ray of a patient with a pituitary
tumour has an enormously enlarged pituitary
fossa. (black arrows).
The posterior clinoid processes of the pituitary
fossa have been eroded.
(b)
(b) skull X-ray showing the presence of a
claficied meningioma (blue and red arrows)
And a normal sized pituitary fossa for
comparison (black arrows)
Some pituitary tumours secrete excess amounts
of either GH (growth hormone) or ACTH
(adrenocorticotrophic hormone).
Some do not secrete excess hormone and cause
symptoms because of pressure effects on
adjacent structures.
The tumours are benign.
Occasionally a tumour may produce an excess
of prolactin – (a prolactinoma)
(a) x20
5(a) This is a microscopic section from a
pituitary adenoma removed from a patient who
had symptoms of over secretion of GH.
All pituitary tumours have a similar pattern on
H&E stained sections, as shown here.
The pattern of packeting of the tumour cells
surrounded by connective tissue strands is a
feature common to most endocrine tumours.
(b) x20
5(b) An immunostain for GH on this tumour
shows positive staining by the tumour cells.
Acromegaly
When a pituitary adenoma arises during adult
life, the clinical condition of acromegaly
occurs.
It is characterized by the presence of large lips,
prominent frontal sinuses, enlargement of the
mandible so the lower jaw over rides the upper
jaw resulting in mal occlusion of the teeth.
The hands and feet become larger than normal,
and there is organomegaly seen best in the
enlargement of the heart.
These changes occur slowly over time and the
patient is usually not aware of them.
4
It is usually a medical attendant or a relative
who has not seen them for some time who
recognizes the changes.
A review of family photographs usually reveals
the subtle changes.
(a)
6(a) This young woman has acromegaly. Her
lips and nose are enlarged and her orbital ridges
are prominent.
long bones have fused, the GH causes the bones
to continue to grow.
The patient is much taller than his or her
siblings.
The hands, feet and organs increase in size and
the facial features of acromegaly occur as well.
Even though the patient is a giant, the muscles
are weak.
(a)
(b)
(b)
6(b) This lateral X ray shows elongation of the
ramus of her mandible.
This caused trouble with her bite because her
upper and lower teeth did not occlude correctly.
8(a) and (b) This young man is seen with his
mother. His gigantism is obvious and his hands
are greatly enlarged.
The enlarged hands are often described as being
‘spade like.’
6(c) Family photographs from the age of 16 to
31 show that the changes began to occur from
her early twenties.
The changes of gigantism can also be followed
by examining family photographs as in the
following example.
(a)
(a)
(b)
(b)
7(a) and (b) This woman, too has acromegaly.
Note her large lips and supra orbital ridges and
her enlarged hands (b).
She has both neurological and endocrine
symptoms of her pituitary adenoma.
She has been asked to look to her left while
keeping her head still. Only the right eye has
moved.
The lateral rectus muscle of her left eye is
paralysed because the VIth cranial nerve that
supplies that muscle has been compressed by
the pituitary adenoma expanding laterally from
the confines of the pituitary fossa.
This nerve runs along the base of the brain from
the lower border of the pons to the orbit via the
dura mater that covers the lateral side of the
pituitary fossa.
(c)
9(a), (b), (c) This is a series of family
photographs of a woman who presented for
medical attention when she was 23 years old.
In (a) and (b) she is seen with her non identical
twin.
In (c) she is with her mother and sister at the
baptism of her niece.
Throughout her life she had been the tallest girl
in the country town in which she lived.
She had gigantism as confirmed by the
presence of increased GH in her plasma and an
enlarged pituitary.
She had a GH producing pituitary tumour
removed.
Hypopituitarism
Gigantism
Gigantism results when the adenoma develops
before puberty and before the epiphyses of the
Primary hypopituitarism
Primary failure of the pituitary results in the
non development of secondary sexual
5
characteristics, and the patients may be of
normal stature or be shorter than normal.
(a) and (b)
(c) and (d)
10(a), (b), (c), (d) This young adult man has no
facial, and only minimal body hair.
His body habitus is not as muscular as would be
expected in comparison with his siblings and
contemporaries.
His voice was relatively high pitched.
He was diagnosed as having hypopituitarism.
Acquired hypopituitarism
This occurs when the pituitary is destroyed by
some pathological process.
Two such processes will be demonstrated
Infarction from excessive blood loss during
the birth of a baby
Destruction by a secondary tumour.
Excessive post partum haemorrhage sometimes
results in infarction of the anterior lobe of the
pituitary.
This may result in death during the first week
following the delivery.
Alternatively the changes are more insidious
and the woman
fails to lactate
develops lack of energy, increase in weight and
loss of body hair
caused by deficiencies of thyroid and adrenal
cortical hormones.
This is called Sheehan’s syndrome after the
pathologist Harold Sheehan (1900 – 1988) who
identified the condition when he was working
in the Womens’ hospital in Glasgow, Scotland,
in the 1930’s.
(a) x1
11(a) This pituitary was obtained from a post
mortem performed on a 24 year old woman
who had a difficult delivery with excessive
blood loss.
A few days after delivery she lapsed into coma
and died soon after being admitted to a
specialist referral hospital.
A is the anterior lobe and it is almost
completely infarcted.
It was soft to feel, and it when it was cut to
make a microscopic section it fragmented.
P is the posterior lobe and it is normal, because
it has a different blood supply from that of the
anterior lobe.
The black arrow is the pars intermedia.
The blue arrow indicates an area of neutrophil
infiltration into the dead tissue.
The red arrow indicates an area of
haemorrhage.
The brown arrow indicates the capsule of the
pituitary which is preserved and stains red.
The green arrow indicates a small peripheral
zone that contains some still viable pituitary
tissue that is supplied by blood from the
capsule.
(b) x10
11(b) This view shows the infarcted cells in the
anterior lobe of the pituitary. (The small dots
are staining artifacts and not cell nuclei.)
(c) x10
11(c) This view shows the infarcted anterior
lobe (A),
the pars intermedia (I)
and the posterior lobe (P).
Both I and P are not infarcted because they
have a different blood supply from the anterior
lobe.
(d) x2
11(d) This is a view from the area marked by a
green arrow in 11(a).
This small area of anterior lobe is situated just
beneath the capsule of the pituitary and is
supplied with blood from the capsule. These
cells have thus managed to survive.
(e)x20
11(e) Surviving cells at the area marked by the
green arrow.
6
(f) x20
Normal thyroid
11(f) The tissue just a little deeper in the gland
is completely necrotic.
Destruction of the pituitary by a secondary
tumour.
(a)
(b)
12(a) and (b) A 23 year old male noticed loss of
libido, loss of body hair and atrophy of his
genitalia over a period of 2years before
presentation.
Investigations showed the presence of a tumour
that was destroying his pituitary.
(a)
(b)
13(a) and (b) This brain from another patient
shows what had happened to the man illustrated
in 12. A tumour of the pineal gland (green
arrow on the left) had extended into his
pituitary (green arrow on the right) destroying
it.
14 Anterior view of a larynx with a normal
thyroid gripping the trachea (brown arrow)
It consists of two lateral lobes (red arrows),
an isthmus (dark blue arrow)
and a pyramidal lobe (light blue arrow)
The green arrows mark the two cartilage
laminae of the thyroid cartilage.
The yellow arrow is the epiglottis.
Iodine deficiency goitre
Iodine deficiency causes multinodular goitres,
and this is by far the most common form of
goitre.
Such goitres are most prevalent in parts of the
world where there are high mountains where
iodine has been leeched from the soil.
The prevalence of iodine deficient goitres can
be greatly decreased by adding iodine to the salt
in these countries.
Untreated iodine deficiency goitres become
very large, and the women with them readily
seek treatment that removes the unsightly
goitre.
(a)
Thyroid
(b)
The commonest abnormality of the thyroid is a
goitre which is defined as a palpable
enlargement of the thyroid gland.
Thyroid diseases occur predominantly in
women.
Types of goitre
Physiological
In women at puberty and during pregnancy.
Pathological
Iodine deficiency
Tumours (benign and malignant)
Thyroid hyperplasia.
Immunological
Thyroxicosis (toxic goitre)
Hashimoto’s thyroiditis
Unusual causes
For example, amyloid goitre
15(a) and (b)
(a) This woman was photographed in 1954 in
the highlands of Papua New Guinea, when the
Stone Age people of this area were having their
first contact with 20th century medicine.
(b) This is a very large goitre (600 grams
weight) from an indigenous woman who lived
in the southern highland area of South India. It
is a surgical specimen from the early 1950’s.
In areas of iodine deficiency, the goitrous
women have marginally normal thyroid
function as demonstrated by tests conducted
during epidemiological investigations.
7
A significant number of children born to such
goitrous women are endemic cretins.
Endemic cretins
This is an iodine embryopathy resulting from
iodine deficiency in the mother.
They do have thyroid tissue and occasionally
they have a goitre.
Clinical features of endemic cretins
fairly characteristic facial features
mental deficiency
short stature
a stiff back
a gait in which they walk with bent knees.
(a) and (b)
16(a) Two endemic cretins with their mothers
in PNG in 1966. The one in the foreground
illustrates the characteristic stance.
16(b) An endemic cretin in the highlands of
PNG with the mountains behind.
In this Stone Age culture it was possible for a
severely handicapped person like this to be
nurtured and to survive.
Sporadic cretins
In this condition the baby is born with no
thyroid tissue,
is severely mentally defective
and fails to develop normally.
Most of the goitres in countries with well
funded medical services are also caused by
iodine deficiency, but the goitres are much
smaller than those seen in poorer iodine
deficient areas.
18 This middle aged Australian woman
illustrates the size of non neoplastic goitres
encountered in countries with well funded
medical services.
Complications of goitres
Unacceptable appearance
They may extend behind the sternum and cause
pressure symptoms, particularly shortness of
breath and cyanosis from compression of the
neck veins at the thoracic outlet when the
woman lifts her arms above her head.
19 Chest X ray showing a retrosternal extension
of a multinodular goitre that contains areas of
calcification. (white arrow).
Multinodular goitres
20 A lateral lobe of thyroid removed as
treatment of a multinodular goitre.
The cut surface shows a nodular pattern and
follicles and small cystic areas filled with
colloid.
(a) x1
(a) and (b)
(b) x2
17(a) A sporadic cretin in Australia. She had
been mentally defective since birth and at 2
years of age she cannot stand unaided.
(c) x4
17(b) A 67 year old female sporadic cretin in
Australia.
She had been in institutional care almost since
birth.
Thyroxin treatment had had no effect on her
profound mental deficiency.
21(a), (b), (c), (d) Microscopic section of this
goitre shows follicles which vary in size, and
contain a variable amount of colloid
(thyroglobulin) stored in each follicle.
The thyroid follicles are lined by a single layer
of cuboidal cells with a regular nuclear pattern.
Goitres in relatively affluent countries
Follicular adenomas
(d) x10
8
Some nodules in a multinodular goitre are more
cellular than those in the previous example, and
sometimes the thyroid enlargement is due to an
apparently single nodule.
Such nodules may be called follicular
adenomas.
22. A follicular adenoma. As part of the pre
surgical workup of a goitre, an FNA (fine
needle aspiration) for cytological examination
is done to try to assess the likelihood of its
being a carcinoma.
In this specimen a needle track made by the
FNA examination can be seen (red arrow).
(a) x1
(b) x2
(c) x10
23(a), (b), (c) Microscopic sections of this
follicular adenoma of the thyroid.
Blood in the FNA track can be seen in (a) (red
arrow).
Thyrotoxicosis
This is a condition in which the thyroid gland
secretes an excess of thyroxin.
It occurs predominantly in middle aged women,
but as shown here, men may be affected.
It has an autoimmune pathogenesis.
The clinical features include,
hyperactivity,
excessive protrusion of the eyes
(exophthalmos)
rapid pulse and cardiac arrhythmias,
heat intolerance,
diarrhoea,
and sometimes psychiatric disorders.
The thyroid is usually mildly enlarged, feels
warm and a bruit can be heard with a
stethoscope placed on it.
24 This man has bilateral exophthalmos from
thyrotoxicosis.
His thyroid is not easily visible.
He had other symptoms of this condition and
his thyroid function tests supported the
diagnosis.
Hashimoto’s thyroiditis
This is an autoimmune disease of the thyroid
characterized by the development of a goitre of
moderate size in middle aged women. (It is
very rare in men)
They have mild hypothyroidism and have
circulating antithyroid antibodies.
Treatment with replacement thyroid hormone is
effective.
25 A female aged 53 presented with a goitre.
Thyroid function tests showed a mild degree of
hypothyroidism and positive thyroid antibodies.
A diagnosis of Hashimoto’s thyroiditis was
made and she responded to thyroid
supplementation therapy.
26 This is a thyroid surgically removed from a
different patient with Hashimoto’s thyroiditis.
(Surgery is not always performed because
medical treatment with replacement thyroxin is
usually effective.)
The cut surface shows a rather ‘meaty’ looking
nodular appearance and reduction in thyroid
colloid.
(a) x1
(b) x2
(c) x10
27(a), (b), (c)
(a) and (b) The microscopic section shows blue
staining areas of cellular lymphoid infiltrations
and a reduced number of colloid filled follicles.
(c) There are areas of follicular epithelial cell
proliferation in which the follicle cells are
enlarged and have pink staining cytoplasm.
These microscopic features are typical of
Hashimoto’s thyroiditis.
Amyloid goitre
This is one of the unusual causes of goitre.
9
28 This teenage girl from Papua New Guinea
presented with a goitre that felt very hard.
The surgeon thought it was a thyroid cancer and
he proceeded to remove it.
Grossly the thyroid felt hard and rubbery. Its
cut surface showed virtually no colloid and it
was a cream colour.
These symptoms were reversed by treatment
with thyroid replacement therapy.
Thyoid cyst.
Cysts result from necrosis of thyroid tissue in
multinodular goitres.
(a)
(a) x1
(b) x1
29(a) This section taken from the amyloid
goitre shows homogeneous areas of pink
staining along the lower right side. This is all
amyloid. The paler areas consist of destroyed
thyroid follicles with amyloid infiltrating the
thyroid and compressing the follicles.
(b) x2
(c) x10
29(a) and (b) A 45 year old female presented
with an enlargement of the left lateral lobe of
the thyroid.
Ultrasound examination revealed the presence
of a cyst which was excised.
Gross examination (a) showed a cyst filled with
clear fluid with a dense fibrous capsule
surrounded by normal thyroid tissue.
The cyst wall and the adjacent normal thyroid
can be seen in the microscopic section. (b).
(d) x20
Thyroid malignancies
29(b), (c), (d) These views show the thyroid
follicles being compressed and destroyed by
pink staining amyloid that gave a green
birefringence when stained with congo red
stain.
Further investigations revealed that the patient
had disseminated primary amyloidosis.
Primary amyloidosis is relatively common in
PNG.
Myxoedema
This is a condition of hypothyroidism which
usually affects middle aged women.
Clinical features
The patients become lethargic
unable to tolerate cold
they become obese,
develop puffiness around the eyes
menstruation ceases
and they suffer from constipation.
30 This middle aged woman has myxoedema.
She had become moderately obese, her
mentation had decreased and she was fatigued.
Papillary carcinoma
This is the commonest type of thyroid cancer.
It occurs in younger patients usually less than
40 years, mostly women.
It presents either as a single nodule, multiple
nodules throughout the whole gland, or as
enlarged cervical lymph nodes resulting from
secondary metastases.
It is slowly progressive with secondaries
particularly in lymph nodes, bone and lung.
Microscopically it has a papillary pattern and
focal areas of calcification are scattered through
the tumour.
Frequently the tumour cells have a distinctive
vacuolation of their nuclei.
32 A male 18 years presented with unilateral
enlargement of the thyroid.
Hemithyroidectomy was performed.
When the specimen was sliced, a well
circumscribed nodule of firm tissue was seen.
(red arrow)
Microscopic examination showed that it was a
papillary carcinoma.
10
Completion thyroidectomy was performed, but
no further areas of tumour were found.
(a) x1
33(a) The section taken from the tumour shows
a papillary tumour (red arrow) with a fibrous
capsule (blue arrow) that separated it from the
normal thyroid. (green arrow)
Microscopically the tumours closely resemble
normal thyroid tissue.
Invasion of veins in the capsule of the tumour,
and metastases are the indications of
malignancy.
35 A follicular carcinoma removed as a single
nodular enlargement of one lobe of the thyroid.
(a) x1
(b) x4
(b) x2
(c) x10
(c) x20
33(b) and (c) show the fibrous capsule in which
there is infiltrating tumour.
The blue arrow in (c) shows another
microscopic feature of papillary carcinoma small calcified areas that are called ‘psammoma
bodies.’
(d) x10
(e) x20
33(d) and (e) These images show the
cytological pattern of the papillary tumour.
The cells are small and regular.
Some of the nuclei are vacuolated in their
centres. This feature is very prominent in many
papillary carcinomas of the thyroid.
34 An enlarged cervical lymph node when cut
across showed the presence of a nodule of
colloid material.
On microscopic section it showed the presence
of secondary papillary carcinoma of the
thyroid.
Follicular carcinoma
This is the second most common type of
thyroid carcinoma.
It occurs in older people, mainly women.
It presents as a single nodule or as a result of
metastases, most commonly in bone and lungs.
Secondary deposits may occur many years after
the original tumour has been removed.
(d) x10
(e) x20
36(a), (b), (c), (d), (e) Microscopic appearances
of a follicular carcinoma of the thyroid.
The follicles and the epithelial cells that line
them are not different from those of a normal
thyroid.
However, one needs to examine the capsule of
the tumour - black arrow in (a) and (d) to look
for the presence of venous invasion to make a
diagnosis of malignancy.
Invasion of a vein can be seen in (d) and (e).
37(a) A woman aged about 40 years presented
with a mass above the forehead. Her primary
thyroid lesion is just noticeable as a mild
enlargement of the left lobe of her thyroid.
37(b) The plain X-ray of the skull showed a
lytic lesion at the site of the tumour. (red arrow)
Biopsy confirmed it as being a secondary
carcinoma of the thyroid.
The metastatic deposit looked like normal
thyroid tissue, as is usually the case in
secondary deposits of follicular carcinoma of
the thyroid.
Medullary carcinoma
This is a rare tumour of the thyroid and it
occurs in older people mainly women.
Microscopically it consists of groups of poorly
differentiated cells which are derived from C
11
cells which are dispersed among the epithelial
cells that line the thyroid follicles.
It is further characterized by the presence of
amyloid deposited throughout the tumour.
It progresses slowly with metastases occurring
many years after excision of the original
tumour
Mostly the tumour presents as a solitary mass
in the thyroid.
Other associated features may accompany
medullary carcinoma
Some tumours secrete ACTH which results in
the production of Cushing’s syndrome. This
presentation is also often associated with
diarrhoea.
Less frequently, but interestingly, it tends to
occur in families, and to be associated with one
of the recognized multiple familial endocrine
adenoma syndromes.
Its most common manifestation in this regard is
with the presence of a phaeochromocytoma
which is frequently bilateral.
(a) x1
(b) x10
(c) x20
38(a) (b), (c) Microscopic views of a medullary
carcinoma of the thyroid showing
undifferentiated tumour cells with occasional
multinucleated cells.
Large deposits of pink staining amyloid can be
seen throughout the tumour.
Multiple familial endocrine adenoma syndrome
One example of this is illustrated in Fig. 39.
39 In this montage, one sees a thyroidectomy
specimen (green arrow) and a cut surface of the
medullary carcinoma (blue arrow).
The patient also had bilateral adrenal
phaeochromocytomas. (red arrows).
Parathyroids
There are four small normal parathyroid glands
attached to the posterior surface of the thyroid,
two upper and two lower.
They secrete parathyroid hormone, which
controls calcium levels in the blood by
increasing phosphate excretion from the
kidney
and Ca absorption from the renal tubules and
from the bowel.
The PAH also helps to control bone turnover in
the skeleton.
Clinical conditions that occur
excessive secretion of PAH
(hyperparathyroidism)
decreased secretion (hypoparathyroidism)
Hyperparathyroidism is by far the more
common clinical problem.
Causes of hyperparathyroidism
The formation of a tumour in one of the glands
- parathyroid adenoma.
Enlargement and hypersecretion of all 4 glands
– parathyroid hyperplasia.
Types of hyperparathyroidism
Primary hyperparathyroidism when there is no
recognizable cause for this.
Secondary hyperparathyroidism which results
from chronic renal failure.
Tertiary hyperparathyroidism occurs when one
or more of the hyperplastic glands becomes
autonomous in its secretion of PAH.
Clinical presentations
The commonest presentation is with an elevated
Calcium (Ca) which is asymptomatic, and
detected on a routine biochemical screening for
some other reason.
Advanced cases present with either bone
lesions or with renal calculi.
Other symptoms are much less frequent.
Treatment
Surgical removal of the adenoma, or most of
the hyperplastic glandular tissue if it is a
hyperplasia.
12
40 Larynx viewed from the posterior aspect.
Red arrows - the two lateral lobes of the thyroid
gland wrapping around the trachea (brown
arrow)
The parathyroid glands are found on the
posterior surface of the larynx beneath a layer
of soft fascia on the most medial border of the
posterior lobes of the thyroid gland.
They are not easy to dissect, and the upper pair
are more easily identified than are the lower
pair. (black arrows).
The sites where the lower pair can be found are
marked by green arrows.
The epiglottis is marked by a yellow arrow.
Usually one finds a small amount of normal
parathyroid tissue adjacent to the surgically
removed adenoma.
Parathyroid adenoma
(d) x4
41 Thyroid viewed from the anterior aspect.
There is a parathyroid adenoma replacing the
left lower parathyroid gland. (green arrow).
The red arrow shows a pyramidal lobe of the
thyroid gland.
(e) x10
42 Male 62. Operative photograph showing the
removal of a parathyroid adenoma. (green
arrow)
The lateral lobe of the thyroid (black arrow) has
been reflected upwards to reveal the adenoma.
The adenoma is still attached by a blood vessel.
Parathyroid hyperplasia
(b) x2
(c) x10
45(b) and (c) show the microscopic
appearances of the normal gland.
It consists of chief cells and a few clusters of
oxyphil cells with pink cytoplasm.
There is a considerable amount of fat between
the cell clusters.
45(d) and (e) show the microscopic features of
the adenoma. It consists of chief cells and a few
clusters of oxyphil cells, best seen in (e).
46 Parathyroid hyperplasia. All 4 glands are
markedly enlarged and most of the tissue from
each gland has been removed by the surgeon.
Bone changes in hyperparathyroidism
43 In this case the surgeon has done a total
thyroidectomy with removal of a right lower
parathyroid gland adenoma (red arrow) and
portions of the other 3 normal parathyroid
glands.
The surgeon aims to leave enough parathyroid
tissue to maintain a normal level of PAH post
operatively.
If too much parathyroid tissue is removed, the
patient develops tetany because the Ca level is
too low.
x1
45 Microscopic sections of the four glands for
comparison with the surgical specimen.
(a) x4
(b) x10
47(a) and (b) A section of bone from a patient
with chronic renal disease and secondary
hyperparathyroid hyperplasia.
It shows the changes of renal osteodystrophy.
The bone trabeculae are thickened, there is an
increase in fibrous tissue in the marrow space.
There is also increased bone turnover as shown
by the presence of osteoclasts (black arrows)
which are actively causing bone resorption, and
osteoblasts (green arrow) which are actively
causing bone formation.
(a) x1
(c) x10 Von Kossa stain
45(a) Parathyroid adenoma on the right with a
remnant of the normal gland on the left.
13
47(c) In renal osteodystrophy there is also an
element of osteomalacia present, as shown by
the prominence of osteoid seams lining the
surfaces of the bone trabeculae. (black arrows)
The bone, which contains calcium, stains black
in this stain.
Note the anatomical positions of the adrenal
glands.
The right one is triangular in shape and the left
one is oval.
(a) x2
Adrenal glands
(b) x4
There are two adrenal glands each situated on
the upper poles of the right and left kidneys.
The right adrenal is triangular in shape and the
left one is oval.
When cut across, they demonstrate the presence
of two layers, an outer cortex and an inner
medulla.
Macroscopically the cortex is yellow because of
the lipid in the cells, and the medulla is a grey
colour (See Fig. 61)
Microscopically the cortical layer is further
divided into 3 layers, from outer to inner - the
glomerular, fascicular and reticular layers.
The cells of the glomerular layer secrete
aldosterone which is involved in the control of
salt and blood pressure.
Its secretion is controlled by the angiotensin
renin hormones from the juxtaglomerular
apparatus in the kidneys.
The cells of the reticular layer secrete cortisone
and sex hormones.
The cells of the fascicular layer are reserve cells
for the reticular layer.
The medulla is related to the autonomic system
and it secretes adrenalin and noradrenalin.
(c) x10
(d) x20
(e) x10
(f) x20
49(a), (b), (c), (d),(e), (f) Microscopic section
showing the morphology of the various layers
of the adrenal gland.
Black arrow capsule.
Blue arrow glomerular layer
Yellow arrow facicular layer.
Green arrow reticular layer.
Red arrow adrenal medulla.
Note in (d) the reticular layer cells contain a
large amount of brown lipofuscin pigment.
In adrenal hyperplasia the glands are enlarged
and the cut surface shows a homogeneous
brown colour due to the hyperplasia of the
reticular layer cells.
Note in (e) and (f) that the cells of the
glomerular layer are arranged in small groups
and they have small nuclei. The layer is not a
continuous one.
(a)
(b)
48(a) and (b) Anterior and posterior views of
the kidneys of a 3 year old child who died from
adrenal failure caused by bilateral adrenal
haemorrhage as a result of meningococcal
septicaemia.
This is an uncommon complication of
septicaemia that results from a number of
different bacterial infections, the commonest
being meningococcal meningitis.
Diseases of the adrenal glands are associated
with the overproduction or underproduction of
hormones that are normally secreted by them.
The main diseases are as follows:
Cushing’s syndrome
Is caused by an overproduction of
corticosteroids (mainly cortisone).
This may result from
14
a primary tumour or primary hyperplasia of
the adrenal cortical cells.
Secondary hyperplasia caused by endogenous
increase in ACTH
from a pituitary tumour,
from iatrogenic administration of ACTH,
or from secretion by a non endocrine tumour
such as a small cell carcinoma of the lung and a
medullary carcinoma of the thyroid.
Addison’s disease
Caused by an undersecretion of adrenal cortical
hormones.
This may be caused by an immunological
abnormality or
By destruction of the adrenal substance by such
lesions as tuberculosis or secondary tumour.
(Secondary lung cancer being the commonest.
tumour to do this.)
Phaeochromocytoma is a tumour of the adrenal
medulla. It secretes adrenalin and noradrenalin.
Adrenocortical tumours that secrete abnormal
amounts of sex hormones, either male or female
hormones.
Hyper aldosteronism
This is a very unusual condition caused by
secretion of aldosterone by a tumour of the
adrenal cortex - a small benign adenoma.
Depression of immunological defence
mechanisms and lowered resistance to
infection.
Other symptoms such as psychiatric reactions
and osteoporosis may also occur.
(a)
50(a) A 45 year old female with Cushing’s
syndrome. She shows the truncal obesity and
abdominal striae of this condition.
(b)
50(b) The photograph on the left was taken 14
months before she presented for investigation.
(c)
50(c) Seven months after removal of an adrenal
cortical adenoma. She has lost the clinical
abnormalities caused by the adrenal tumour.
(a)
51(a) This is a 4 year old female child with
Cushing’s syndrome.
(b)
51(b) The same child aged 3 years.
Another important tumour of the adrenal gland
is the neuroblastoma, a tumour which arises
from the adrenal medulla in very young
children with a mean age of about 3 years.
This does not secrete hormonal substances but
it is one of the commoner tumours of
childhood.
(c)
Cushing’s syndrome
This occurs in both sexes at all ages.
It presents with changes in bodily appearance
Truncal obesity
Stretch marks (striae) on the abdomen,
Red cheeks with a round face.
Hirsutism (increased facial hair in females)
Hypertension
This is the name given to the disease that
results from loss of all the hormones secreted
by both the cortex and the medulla of the
adrenal gland.
Those affected complain of weakness and
tiredness.
They may be dehydrated and they notice an
increased pigmentation of the skin, and buccal
mucosa.
The investigations are listed in the appendix.
51(c) The same child aged 5 years one year
after removal of one adrenal gland that was the
site of adrenal cortical hyperplasia.
Addison’s disease
15
Untreated it leads to death, but it can be
controlled by adequate hormone replacement
therapy.
The causes are
An auto immune reaction
Replacement of the adrenal glands by infection
(tuberculosis or fungus) and by secondary
tumour.
These features are illustrated in the following
cases.
(a)
adrenal failure which is accompanied by an
excessive pigmentation of the skin.
Adreno cortical tumours that secrete sex
hormones.
(a)
56(a) An 11month old male with a lump in the
right upper quadrant of the abdomen and an
enlarged left lobe of liver. These are marked on
his abdomen.
Investigations revealed that the lump was an
adrenal tumour.
(b)
(b)
52(a) and (b) A male aged 21 years. He worked
as a builder’s labourer and was suffering from
progressive weakness and lethargy.
He had been hyperpigmented for 2 years.
Hyper pigmentation of the palmar creases of his
right hand can be seen.
He also had pigmentation of his buccal mucosa.
A diagnosis of auto immune Addison’s disease
was made.
Following hormone replacement therapy, his
pigmentation and other symptoms of tiredness
regressed.
This type of Addison’s disease results in
atrophy of both adrenal glands.
54(b) Close up of the genitalia showing
abnormally precocious development.
(c)
56(c) An operative photograph showing the
adrenal tumour (black arrow), normal left lobe
of the liver that was pushed aside by the adrenal
tumour (white arrow).
The red arrow indicates the right kidney.
The tumour was removed and his symptoms
and signs regressed. He was alive and well at
10 year follow up.
Tumours of the adrenal medulla
53 The adrenal gland on the right is of normal
size while that on the left is from a patient who
died from Addison’s disease. It is small and
atrophic.
54 Both adrenal glands from this patient who
died from disseminated tuberculosis are almost
completely destroyed by infiltration by the
tuberculous granulation tissue.
55 Both of these adrenal glands contain
secondary deposits from a primary lung cancer.
(green arrows)
This is a common site of secondaries from lung
cancer.
Sometimes the tumour deposit is so extensive
that the adrenals are virtually destroyed, and in
the few weeks before death the patient develops
Neuroblastoma
Phaeochromocytoma
Neuroblastoma
Neuroblastoma is one of the more common
tumours that occur in childhood.
It may be present at birth but its average age of
onset is 3 years.
It does not secrete any hormonal substance but,
untreated it is a highly aggressive tumour
metastasising to para aortic lymph nodes, liver
and lung.
57 The mother of this 6 year old male child felt
a lump in the right upper quadrant of his
abdomen.
The tumour was removed surgically.
16
No metastatic disease was found during this
admission.
(a)
58(a) This child died a few days after birth. The
post mortem examination revealed a tumour
replacing the left adrenal gland (green arrow).
The right adrenal gland is normal. Lungs, liver
and other organs had metastatic tumour
deposits in them.
(b)
58(b) The left adrenal and kidney were
removed together, and the whole specimen was
sliced vertically.
The cut surface of the tumour (red arrows) is
black from haemorrhage, but white
homogeneous areas of tumour can be seen.
It may be difficult at macroscopic examination
to distinguish adrenal haemorrhage from
haemorrhage into an adrenal tumour.
59 This is a post mortem specimen from a
female aged 1 year who died from disseminated
neuroblastoma. It is viewed from its posterior
aspect.
The specimen has been sliced to show the
primary tumour in the left adrenal (blue arrow)
and the extensive metastatic spread to the
paraaortic lymph nodes. (yellow arrows).
The haemorrhagic nature of the tumour can be
seen by the black coloured blood within the
tumour.
Black arrows kidneys.
Red arrow aorta.
Green arrow normal right adrenal gland.
x 20
60 This is a microscopic section of the
preceding neuroblastoma. It consists of sheets
of small cells with little cytoplasm and regular,
deeply staining nuclei.
Phaeochromocytoma
These tumours arise from the tissue of the
adrenal medulla.
They nearly always secrete hormone –
adrenalin and noradrenalin. This causes
hypertension which characteristically occurs
intermittently.
The patient recognizes the presence of
hypertension by the occurrence of headaches,
palpitations and shortness of breath from
incipient heart failure.
In modern hypertension clinics, investigations
are revealing the presence of
phaeochromocytomas at an earlier stage of
development, and the treatment is instituted
earlier than before.
Operation used to be fraught with some
difficulty because it was not possible to
ascertain beforehand which side the tumour was
on.
Palpation of the tumour during operation results
in a surge of adrenalin and a high blood
pressure which causes problems for the
anaesthetists and risk for the patient.
Modern imaging techniques are more sensitive
and make it possible to be more accurate in
identifying the side of the tumour.
As mentioned already in this chapter,
phaeochromocytomas may arise in association
with some of the so called multiple endocrine
adenoma syndromes.
61 Adrenalectomy for a phaeochromocytoma in
a female aged 25 years.
The tumour (black arrow) can be seen arising
from the medulla.
She presented with the usual symptoms of
intermittent episodes of headache and
tachycardia with incipient heart failure.
Her symptoms disappeared after removal of the
tumour.
Note the remaining normal adrenal gland (red
arrow). The yellow cortex and grey medulla are
clearly shown.
Endocrine diseases of the gonads.
The gonads may fail to mature and this results
in failure of the secondary sex characteristics to
develop – a condition called primary
hypogonadism.
17
Tumours of the gonads may secrete excessive
amounts of either of the sex hormones.
(a)
(b)
62(a) and (b) A female aged 8 years presented
because her mother noticed a lump in her lower
abdomen. (a)
She did not notice the precocious breast (a) and
vulval (b) development of precocious puberty.
(a)
63(a) Operation revealed a large tumour
replacing the left ovary. (red arrow)
Its surface was smooth and no other tumour
was identified.
The uterus, (yellow arrow)
the right ovary (blue arrow)
and both Fallopian tubes (black arrows)
were normal, as can be seen in the operative
photograph.
(b)
63(b) The tumour was a granulosa cell tumour
and this image shows its cut surface which is
partially solid and partially cystic.
These tumours frequently secrete oestrogen.
When they occur before puberty they cause
precocious puberty as in this case.
When they occur during reproductive life they
cause menorrhagia.
After menopause they cause post menopausal
bleeding.
They may be benign or malignant.
64 At follow up 6 years after operation the
patient was well and her symptoms and signs
had resolved.
x1
65 Orchidectomy for a testicular tumour which
on histological examination was seen to be
composed of Leydig cells.
These cells are normal constituents of the testis
and they secrete testosterone.
Sometimes the tumour secretes excess
testosterone, with symptoms of precocious
puberty in children, or increased libido in adults
Sometimes it secretes oestrogen and this causes
gynaecomastia..
The blue arrow indicates the tumour.
The red arrow indicates the tunica albuginea
which covers the testis.
The green arrow indicates the seminiferous
tubules which are being compressed by the
tumour, and at higher magnification it was seen
that the tubules were undergoing pressure
atrophy.
Teratomas of the testis may also secrete sex
hormones.
Pancreas
The pancreas has two main functions, an
exocrine one in which it is a source of digestive
enzymes.
And an endocrine one in which it secretes
insulin and glucagon.
The digestive enzymes are produced by the
glandular (acinar) portion of the gland, and the
hormones are secreted by the cells of the islets
of Langerhans.
(a) x2
(b) x4
(c) x10
66(a), (b), (c) show the microscopic
appearances of the pancreas.
The islets of Langerhans (black arrows) are
surrounded by the glandular acinar tissue of the
exocrine pancreas.
Within the islets, two types of cell can be
identified, one of which secretes insulin and the
other secretes glucagon.
18
Tumours of the islet cells are rare, but when
they are encountered they may secrete either
insulin or gastrin.
Patients with an islet cell tumour may present
with symptoms of hypoglycaemia or intractable
peptic (stomach) ulcers depending on whether
the tumour is secreting insulin or gastrin.
Diabetes mellitus
is the endocrine disease that occurs when the
islet cells fail to secrete enough insulin. This
failure is most commonly of immunological
origin.
Insulin plays an essential role in carbohydrate
metabolism as well as in other aspects of
energy metabolism, growth and development of
the body.
The main presenting symptoms of diabetes are
polydypsia, (excessive drinking)
polyphagia (excessive eating)
and polyuria (excessive passing of urine.)
In spite of the excessive eating, the patient loses
weight.
Patients are more susceptible to infections than
are normal people.
The metabolic upset causes hyperlipidaemia
which results in a high incidence of
atherosclerotic vascular disease and all its
complications.
Diabetes is divided into two types
Type 1 Juvenile onset which begins in children
and young adults, and requires daily insulin
injections for life.
Type 2. Adult onset which occurs after middle
age and is associated with obesity. It can be
controlled by weight reduction and oral insulin.
Peripheral vascular disease is a frequent cause
of occlusion of small arteries in the toes. This
results in ischaemia and later, gangrene of the
toes. In later stages, gangrene of the foot and
the leg occurs.
(a) and (b)
67(a) and (b)
(a) is the right foot of a 40 year old female
diabetic patient. All her toes are ischaemic.
(b) A 60 year old male diabetic patient with
gangrene of the fourth toe of the left foot.
19
Biochemical tests for endocrine diseases
Acromegaly/Gigantism
1. Serum oestradiol
Investigations
1. IGF-1 (insulin-like growth factor 1)
Normal reference range
Varies with age, gender, pubertal status
Adult 5-30nmol/L
Sample positive result
IGF-1 84nmol/L
2. Oral glucose tolerance test
Normal reference ranges for adults
Early follicular phase 100-200pmol/L,
Preovulatory phase 500-1700pmol/L,
Luteal phase 500-900pmol/L,
Postmenopausal 70-200pmol/L
2. FSH, LH
Normal reference ranges for adults
Premenopausal FSH 1-8U/L, LH 2-15U/L,
Postmenopausal FSH >18U/L, LH 15-100U/L
Normal reference range
Growth hormone (GH) suppresses to <2mU/L
after glucose load
Sample positive result
Nadir of GH 15mU/L after 75g oral glucose
Sample positive results
Male Hypogonadism
Secondary hypogonadism
Serum oestradiol 80pmol/L
FSH 8 U/L, LH 4 U/L
Investigations
Primary hypogonadism
Serum oestradiol 80pmol/L
FSH 55U/L, LH 64 U/L
Total testosterone
FSH (follicle stimulating hormone)
LH (luteinising hormone)
Cushing’s syndrome
Normal reference ranges for adults
Testosterone: 8-35nmol/L
FSH 1-5 U/L
LH 2-10 U/L
1. 24 hour urinary free cortisol
Normal reference range for adults
<150nmol/24 hours
Sample positive result
4000nmol/24 hours
Investigations
Sample positive results
Primary hypogonadism
Total testosterone 2.4nmol/L
FSH 58 U/L, LH 39 U/L
Secondary hypogonadism
Total testosterone 5nmol/L
FSH 5 U/L, LH 8 U/L
Female Hypogonadism
Investigations
0800h serum cortisol 324nmol/L
Sample positive result
2. 1mg overnight dexamethasone suppression
test
Normal reference ranges for adults
0800h serum cortisol suppresses to <100nmol/L
after 1mg dexamethasone 2300h the night
before
Sample positive result
0800h serum cortisol 324nmol/L
20
3. Sleeping midnight plasma cortisol
Normal reference ranges for adults
<50nmol/L
Sample positive result
Loss of circadian rhythm
Precocious puberty
1. Diagnosis is made on clinical grounds.
2. Serum FSH, LH and response to GnRH
(Gonadotrophin releasing hormone) will assist
in differential diagnosis.
Normal reference ranges
Prepubertal – flat response
Pubertal – LH >15U/L, FSH >7.5U/L
Sample positive results
GnRH dependent eg. Pituitary tumour
Post pubertal levels sex steroids,
gonadotrophins not suppressed
GnRH independent eg. Gonadal tumour
Post pubertal levels sex steroids,
gonadotrophins suppressed, and response to
exogenous GnRH suppressed
3. The following may be useful in determining
aetiology of GnRH independent precocious
puberty:
Total testosterone
Normal reference range
Prepubertal <0.5nmol/L
Serum oestradiol
Normal reference ranges
Prepubertal <100pmol/L
Adult male 60-180pmol/L
Androstenedione
Prepubertal : <3nmol/L
Adult female premenopausal 3.5-9.0nmol/L,
Postmenopausal <6nmol/L,
Male 1-8nmol/L
DHEAS (dehydroepiandrosterone sulphate)
Normal reference ranges
Prepubertal : <4µmol/L (varies with age)
Adult : varies with age and gender
Serum hCG (human chorionic gonadotrophin)
Non-pregnant : <5mU/L
Primary Hyperaldosteronism (Conn’s
syndrome)
1. Aldosterone/renin ratio (ARR)
Results are affected by sodium intake, posture
and many drugs
Normal reference ranges
Aldosterone – Adult ambulatory 100900pmol/L,
supine 30-450pmol/L
Plasma renin activity – Adult ambulatory 14ng/ml/h,
supine <2ng/ml/h
ARR 80 / 530
Sample positive results
Aldosterone 1200pmol/L
Plasma renin activity 1ng/ml/h
ARR 1200
2. Fludrocortisone suppression test
Normal reference range
Aldosterone should suppress to <160pmol/L by
day 5
Sample positive result
Aldosterone 320pmol/l after 4 days
fludrocortisone (day 5)
Congenital Adrenal Hyperplasia
Serum 17-hydroxyprogesterone (17-OHP) (+/synacthen stimulation)
Normal reference range
<6nmol/L
Sample positive result
17-OHP 32nmol/L
Addison’s disease
1. Short synacthen test
Normal reference range
Rise in plasma cortisol of >200nmol/L to peak
of >500nmol/L
Sample positive result
Serum cortisol : basal 90nmol/l,
+30min 100nmol/L
+60min 200nmol/L
21
2. ACTH (adrenocorticotrophic hormone)
Normal reference range
10-50ng/L
Sample positive result
ACTH 110ng/L
3. Anti-adrenal antibodies
Normal reference range
Not detectable
Sample positive result
Detectable
Phaeochromocytoma and Neuroblastoma
1. 24 hour urinary catecholamines and
metabolites
Normal reference range
Adults
Noradrenaline <750nmol/d
Adrenaline <80nmol/d
Normetadrenalines <2.3µmol/d
Metadrenalines <1.7µmol/d
HMMA (hydroxymethoxymandelic acid)
<28µmol/d
Sample positive result
Raised urinary excretion of catecholamines and
metabolites,
Raised plasma catecholamines and metabolites,
Non-suppressibility on clonidine suppression
test.
Further dynamic testing eg. Phentolamine test
and glucagon stimulation are not routine
2. Plasma catecholamines
Normal reference range
Adults
Noradrenaline 0.1-6.3nmol/L
Adrenaline 0.1-1.5nmol/L
3. Plasma metadrenalines
Normal reference range
Adults
Metadrenaline 0.06-0.31nmol/L
Normetradrenaline 0.1-0.61nmol/L
4. Clonidine suppression test
Normal reference range
Plasma total catecholamines suppress to
<3nmol/L within 3 hours of 0.3mg oral
clonidine
Hyperparathyroidism
1. PTH (parathyroid hormone)
Normal reference range
1-7pmol/L
2. Ionised calcium
Normal reference range
1.25-1.35 mmol/L
3. Serum phosphate
Normal reference range
0.8-1.5mmol/L
4. Serum creatinine
Normal Child : 0.04-0.08mmol/L
Normal Adult : female 0.05-0.11mmol/L
Normal Adult male 0.06-0.12mmol/L
5. 24 hour urinary calcium:creatinine
Normal 2.5-7.5mmol/24hrs
6. 1,25 (OH)2 Vitamin D
Normal reference range 35-120pmol/l
Sample positive results
Primary hyperparathyroidism
PTH elevated
Ionised calcium elevated
Serum phosphate low
Normal renal function
Normal to raised urinary calcium (if low
consider familial hypocalciuric
hypercalcaemia)
Secondary Hyperparathyroidism
PTH elevated
Ionised calcium normal to low
Serum phosphate normal to elevated
Renal impairment
1,25 (OH)2 Vitamin D low
Tertiary Hyperparathyroidism
PTH elevated
22
Ionised calcium elevated
Serum phosphate elevated
Renal impairment
1,25 (OH)2 Vitamin D low
2.Anti-thyroid antibodies (microsomal, thyroid
peroxidase, thyroglobulin)
Normal reference range
Not detected
Thyrotoxicosis
Sample positive results
Primary hypothyroidism
TSH elevated
Free T4 and T3 low
Anti-thyroid antibodies may be detected in
autoimmune hypothyroidism eg. Hashimoto’s
disease
Thyroid function tests
1. TSH (thyroid stimulating hormone)
Normal reference range
0.3-5.0mU/L
2. Free T4
Normal reference range
9-23pmol/L
3. Free T3
Normal reference range
3.5-5.5pmol/L
4. TSH receptor antibodies
Not detected
5. ESR (erythrocyte sedimentation rate)
Normal reference range
Child: 2-15mm/h
Adult : female 17-50y 3-12mm/h,
>50y 5-20mm/h
Male 17-50y 1-10mm/h,
>50y 2-14mm/h
Secondary hypothyroidism
Free T4 and T3 low with TSH normal to low
Diabetes Mellitus
1. Fasting plasma glucose (FPG)
Normal reference range
FPG >6mmol/L
2. 75g oral glucose tolerance test
Normal reference range
FPG >6mmol/L 2 hour glucose <7.8mmol/L
Sample positive results
Diabetes mellitus:
FPG >7.0mmol/L and/or 2 hour glucose
>11.1mmol/L
Sample positive results
Primary hyperthyroidism eg. Graves’ disease,
thyroiditis
TSH <0.05mU/L
Free T4 and T3 elevated
TSH receptor antibodies and ESR may assist
with determining the aetiology
Secondary hyperthyroidism eg. TSH secreting
pituitary tumour
Free T4 and T3 elevated with TSH normal to
high
Hypothyroidism
1. Thyroid function tests
As listed under thyrotoxicosis
Impaired fasting glycaemia
FPG 6.1-6.9mmol/L, 2 hour glucose
<7.8mmol/L
Impaired glucose tolerance
FPG >7mmol/L, 2 hour glucose 7.811.0mmol/L