Transcript Slide 1

Pituitary problems
Sahaja Gopu
• Pituitary gland – endocrine gland which is pea sized and it sits
in pituitary fossa, which is situated in the sphenoid bone in
the middle cranial fossa at the base of the brain.
• Pituitary gland has two components – anterior pituitary or
adenohypophysis and posterior pituitary or neurohypophysis.
Hormones secreted
Hypothalamus
Pituitary gland
GHRH- Growth Hormone Releasing
Hormone
GH – Growth Hormone
CRH – Corticotrophin Releasing Hormone
ACTH - Induces cortisol release from the
adrenal cortex
GnRH – Gonadotrophin Releasing
Hormone
FSH and LH
Prolactin
TRH –Thyrotophin Releasing Hormone
TSH – Induces thyroid hormone
production by the thyroid
Vasopressin – released by posterior
pituitary
Stimulates conservation
of water by the kidneys
Pituitary tumours
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Tumours are almost always benign and cause effects include –
hyper/hypo pituitarism and local effects.
Different types of tumours Non-functioning adenomas
Prolactinoma
GH-secreting tumours
ACTH-secreting tumours
Thyroid-stimulating hormone-secreting
Leutinising hormone/follicle-stimulating hormone (LH/FSH)secreting tumours.
Metabolic risk factors such as hypertension, hyperlipidaemia and
glucose intolerance are enhanced in many patients with pituitary
disease and should be vigorously addressed
Local effects
• Headache – Usually retro-orbital or bi temporal, worse on
waking. Sudden catastrophic headaches may be result in
acute pituitary failure which is rare medical emergency.
• Visual field defects –Bitemporal hemianopia is classic but any
defect can occur.
• Ocular nerve palsy – squint.
• Disorders of thirst, appetite, temperature regulation may
occur if extended onto hypothalamus.
Hyper and hypo pituitarism
• ACTH producing tumour presents as cushings syndrome.
• GH secreting tumour – Acromegaly and Gigantism in children.
Slowly progressive.
• Prolactima – microadenoma are common.
• Hypopituitarism tends to occur in the following order of
leutinising hormone , growth hormone, thyroid-stimulating
hormone , and lastly adrenocorticotrophic hormone and
follicle-stimulating hormone. Therefore the presentation in
adults tends to be infertility, oligo/amenorhea, decreased
libido and erectile dysfunction. Deficiency of LH and GH may
result in decreased muscle bulk, decreased body hair, central
obesity and small, soft testes. In children,it commonly
presents with delayed puberty or impairment of growth.
Prolactinoma
• Benign tumour
• Prolactin production can be stimulated by various
factors: dopamine receptor antagonists, thyrotropinreleasing hormone (TRH), vasoactive intestinal peptide
(VIP) or epidermal growth factor, and by suckling an
infant ; inhibited by dopamine.
• Classification :Microadenomas: <10 mm.
• Macroadenomas: >10 mm.
• Giant pituitary adenomas: >40 mm.
• Malignant prolactinomas -very rare
Causes of hyperprolactinaemia
• Physiological – pregnancy, puerparium, stress, non fasting sample
• Intracranial causes:
• 1.Prolactinomas: Microprolactinomas -MCC about 90%,
Macroprolactinomas 10%(>10 mm size),Pituitary or hypothalamic tumour
compressing the pituitary stalk, eg craniopharygioma.
• 2.Head injury
• Endocrine causes
• Hypothyroidism (due to increased synthesis of TRH).
• Cushing's syndrome.
• Chronic renal failure
• Severe liver disease
• Polycystic ovarian syndrome
• Drugs
Prolactinoma can also occur in about 20% of patients with multiple
endocrine neoplasia type 1
Drugs causing hyperprolactinaemia
• Dopamine receptor antagonists, eg domperidone,
metoclopramide, neuroleptics.
• Dopamine-depleting agents, eg methyldopa.
• Antidepressants, e.g tricyclic antidepressants, monoamineoxidase inhibitors, serotonin reuptake inhibitors.
• Verapamil.
• Opiates.
• Protease inhibitors.
• Benzofibrate.
• Omeprazole.
• H2-receptor antagonists.
• Oestrogens, anti-androgens.
Prolactinoma
• In women -Infertility, Amenorhea, oligomenorhea,
galactorhea, reduced libido.
• In men symptoms are subtle which include reduced
libido,erectile dysfunction and reduced beard growth.
• Headache.
• Visual disturbances (classically, a bitemporal
hemianopia (lateral visual fields) or upper temporal
quadrantanopia).
• Cranial nerve palsies
• Symptoms and signs of hypopituitarism
• Investigations – exclude pregnancy, TFTs, basal prolactin level.
MRI and visual field testing.
Treatment
• Indications for treatment are: effects of tumour size and
hyperprolactinaemia.
• Treatment -medical with dopamine agonists like cabergoline
or bromocriptine. Others include surgery+/- radiotherapy.
• Cardiac valvopathy and pleural and pericardial fibrosis are
serious side effects of cabergoline.
• During pregnancy there is a small risk of tumour enlargement,
particularly with macroadenomas and if treatment is
required, bromocriptine and cabergoline appear to be safe
during pregnancy.
Hypopituitarism
• Presentation varies from asymptomatic to acute pituitary failure with
acute collapse and coma, depending on the aetiology, rapidity of onset,
and predominant hormones involved.
• May present with endocrine dysfunction:
– Adrenocorticotrophic hormone (ACTH) deficiency:
• Chronic: fatigue, pallor, anorexia, weight loss
• Acute: weakness, dizziness, nausea, vomiting, circulatory collapse,
fever, shock
• Children: delayed puberty, failure to thrive
• Hypoglycaemia, hypotension, anaemia,
lymphocytosis, eosinophilia,hyponatraemia
– Thyroid-stimulating hormone (TSH) deficiency:
• Tiredness, cold intolerance, constipation, hair loss, dry skin,
hoarseness, cognitive slowing
• Weight gain, bradycardia, hypotension
Hypopituitarism
– Gonadotropin deficiency:
• Women: oligomenorrhoea, loss of libido,
dyspareunia, infertility, osteoporosis
• Men: loss of libido, impaired sexual function, mood impairment,
loss of facial, scrotal, and body hair; decreased muscle mass,
osteoporosis, anaemia
• Children: delayed puberty
– Growth hormone deficiency:
• Decreased muscle mass and strength, visceral obesity, fatigue,
decreased quality of life, impairment of attention and memory
• Dyslipidaemia, premature atherosclerosis
• Children: growth retardation
– Antidiuretic hormone deficiency:
• Polyuria, polydipsia
• Decreased urine osmolality, hypernatraemia
– May also present with features attributable to the underlying cause:
• Space-occupying lesion: headaches or visual field deficits
• Large lesions involving the hypothalamus: polydipsia
and inappropriate secretion of antidiuretic hormone
Cushing’s disease
• The most specific signs of Cushing’s disease are proximal
myopathy , facial plethora, easy bruising and reddish purple
striae greater than 1 cm wide and neuropsychiatric problems.
• The best screening test for the presence of
hypercortisolaemia remains sequential 24-hour urinary-free
cortisol measurements. Late night salivary cortisols are
increasingly available.
• Metyrapone 500 mg – 4 g daily in divided doses reliably but
reversibly inhibits adrenal cortisol synthesis and
secretion.Other modes include surgery
• There remains a significant, persistent and unpredictable
tendency to relapse that affects almost one-third of patients
by 10 years
• Sheehans syndrome – pan hypopituitarism
Case
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A previously fit 36-year-old man presented with a 2 year
history of enlarged hands and feet. In particular, he had
noticed that he needed an increased shoe size. He was
otherwise well, with no other symptoms. There was no past
medical history or family history of note. On examination, the
only significant finding was that the man’s hands appeared
disproportionately large and broad and rather ‘spade-like’ in
nature. Otherwise, examination was entirely normal.
Acromegaly
• Prolonged excessive secretion of growth hormone.
• MC cause is pituitary adenoma- 99%
• Mean age of diagnosis is 40-45yrs and delay in diagnosis is
common.
• Common in both sexes and all races.
• It is slow growing tumour and changes in appearance may not
be noticed easily hence comparing with old photographs may
be useful.
Signs and symptoms
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Changes in appearance
Coarse, oily skin—women may also have mild hirsutism
Change in facial features—enlarged suprorbital ridges, wide
nose, prognathism
Increase in foot and hand size (a bigger shoe size is needed or
rings no longer fit)
Skin tags
Increase in teeth spacing
Macroglossia
Pressure effects
Headache
Visual field defects
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Other non specific
Tiredness and lethargy
Deepening of voice
Sweating (50–80%)
Paraesthesiae
Musculoskeletal pain
Menstrual irregularities and/or galactorrhoea (due to
associated hyperprolactinaemia)
Visceral hypertrophy—liver, kidneys, prostate, heart, thyroid
(multinodular go
Conditions associated
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Respiratory - Sleep apnoea (20–80%)
Cardiovascular
Hypertension (40%)
Heart failure
Cardiomyopathy
Arrhythmia
Metabolic
Diabetes mellitus (19–56%)
Lipid disturbances
Hypercalciuria
Musculoskeletal
Osteoarthritis of the back and weight-bearing joints (20–50%)
Carpal tunnel syndrome (20–52%)
Malignancy
Diagnosis and treatment
• In primary care, if a diagnosis of acromegaly is suspected,
check a random growth hormone and IGF-1 level and if
abnormal refer for specialist advice.
• Options – 1.surgery [hypophysectomy]
• 2. medical with somatostatin analogues ie Octreotide
• 3. other dopamine agonists with cabergoline
• Follow up – lifelong with specialist.
• All patients with acromegaly should be offered regular
colonoscopic screening for bowel cancer starting at the age of
40 years.
Akt questions
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A 28 year old woman comes to see you. She feels tired all the time,
and has been seeing the health-visitor who suspects postnatal
depression. She had a post-partum haemorrhage following the
delivery of her first child two years ago. She has put on a stone in
weight, is cold and amenorrhoeic. She is unhappy, but not
depressed. She desperately wants to conceive, and has been trying
for a year. You check a subfertility screen. She is not ovulating. Free
T4 and TSH are both very low, as is Prolactin, LH and FSH. Which
one of the following is the most likely diagnosis?
a ) Cushing’s syndrome
b ) Hypothyroidism
c ) Kallman’s syndrome
d ) Polycystic ovarian syndrome
e ) Sheehan’s syndrome
• A 42-year-old man presents to his GP feeling generally unwell.
For the past three months he has been experiencing daily
frontal headaches which have not been helped by regular
paracetamol. He has also noticed some unusual symptoms
such as his wedding ring no longer fitting, his shoe size
apparently increasing and a small amount of milky discharge
from both nipples. On examination his blood pressure is
168/96 mmHg. What is the most likely diagnosis?
• A 45-year-old man with a history of depression and gastrooesophageal reflux disease presents to his GP due to a milky
discharge from his nipples. The following blood results are
obtained:
Prolactin 700 mu/l
Which one of his medications is most likely to be responsible?
• A Metoclopromide
• B cimetidine
• C Flouexetine
• An 18-year-old male presents to his GP concerned about
delayed pubertal development, despite being 1.77m tall. On
examination he has scant pubic hair and reduced testicular
volume. The following blood results are obtained:
Testosterone6.7 nmol/l (9 - 30)LH3 .1 mu/l (3 - 10)FSH5.7 mu/l
(3 - 10)
What is the most likely diagnosis?
• A kallmann’s syndrome
• B Klienefelter’s syndrome
• C primary testicular failure
• D Testicular feminisation syndrome
• Klinefelter's - LH & FSH raised
Kallman's - LH & FSH low-normal
kallman’s syndrome
• Kallman's syndrome is a recognised cause of delayed puberty
secondary to hypogonadotrophic hypogonadism. It is usually
inherited as an X-linked recessive trait.
• Features include :delayed puberty
• hypogonadism, cryptorchidism
• anosmia
• sex hormone levels are low
• LH, FSH levels are inappropriately low/normal
• patients are typically of normal or above average height
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52-year-old man presents to his GP as he is concerned about
a discharge from his nipples. Which one of the following drugs
is most likely to be responsible?
A Ranitidine
• B Isoniazid
• C Spironolactone
• D Chlorpromazine