PBL 2

Pituitary disease pg1075 Robbins

Clinical manifestation of pituitary disease
Hyperpituitarism
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pituitary adenoma, hyperplasia, carcinoma of anterior pituitary, secretion of

hormones by nonpituitary tumours, hypothalamic disorders

Hypopituitarism
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deficiency of trophic hormones. Can be due to destructive process

(ischaemic, surgery or radiation, inflammatory reactions and nonfunctional
pituitary adenomas).

Local mass effects Bitemporal hemianopia (pressure on optic chiasm) due to

pressure on the sella turcica.
ICP
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Headaches, nausea vomiting

Acute haemorrhage into adenoma

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Pituitary apoplexy

Pituitary adenomas and hyperpituitrarism (do later)

Hypopituitarism
Decrease secretion of pituitary hormones due to disease of hypothalamus or
pituitary. Hypofunction of anterior pituitary occurs when 75% is lost or abent.
Posterior pituitary dysfunction = diabetes insipidus and always hypothalamic origin
Causes
1. Tumours and mass lesions benign tumours arising within the sella, primary
and metastatic maglingancies, cysts.
2. Traumatic brain injury and subarachnoid haemorrhage
3. Pituitary surgery or radiation
4. Pituitary apoplexy sudden haemorrhage into the pituitary gland occurring
in pituitary adenoma
a. Medical emergency
b. Excrucitating headache
c. Diplpia
d. Hypopituitarism
e. Cardiovascular collapse
f. LOS
g. Death
5. Ischamic necrosis of pituitary and Sheehan syndrome
a. Postpartum necrosis of anterior pituitary

b. Pregnancy enlarges the anterior pituitary but not increase in blood

supply thus relative hypoxia. Shock or obstetric haemorrhage can
precipitate infarction of anterior lobe
c. Post partum bleeding
d. Associated symptoms failure to lactate, absent menstruation and
cold intolerance
6. Rathke cleft cyst
7. Empty sella syndrome condition or treatment that results in destruction
of pituitary e.g. surgery or radiation
a. Primary = defect in diaphragm sella and arachnoid mater and CSF
herniate the sella to compress the pituitary. Usually in obese women
with multiple pregnancies, prolactinemia
b. Secondary pituitary adenoma or mass enlarges the sella
8. Hypothalamic lesions Also results in diabetes insipidus
Treatment
Hormone replacement therapy corticosteroids, thyroxine, sex steroids, human
growth hormone

Uptodate
Short child or growth failure
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Chronic systemic disease (liver produces IGF1)

Hypothyroidism
Turners syndrome
Skeletal disorder
Pituitary problem

Tests IGF1 IGFBP3 bone age

PBL1
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When doing bone DEXA for bone age look at the epiphyseal plate. If the plate
is closed, the child cannot grow.
If the plate is still open the child has potential to grow.

Prolactin excess can inhibit LH and FSH.

-

Pituitary adenoma commonly presents as benign with prolactinoma

Treat: dopamine agonist (bromocriptine or cabergoline) and transsphenoidal
resection

This picture shows the release of dopamine and TRH influencing on antioer pituitary
to produce prolactin. Dopamine inhibits the production of prolactin and TRH
increases the production of prolactin. Thereby the negative feedback cycle
potentiates dopamine. Prolactin inhibits GnRH and thus decrease release o FSH
and LH.

Central diabetes insipidus physiology and pathology.

Hypothalamus produce ADH and oxytocin (supraoptic nuclei) transported to

posterior pituitary via neurophysin
ADH
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Regulates serum osmolarity via V2 receptors (DECREASES serum osmolarity

and INCREASES urine osmolarity) via regulation of aquaporin channel at renal
collecting duct
REgualtes blood pressure via V1 receptors
ADH level is decreased in central diabete insipidus and increased in
nephrogenic DI
o Due to mutation in V2 receptor

Treatment: Desmopressin acetate (ADH analog) is treatment for central DI

Learning topic: Growth charts and trajectory before during and after
puberty
Adapted from practical paediatrics
Before puberty
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First years of life = linear growth velocity is rapid around 8-12cm/year.

Childhood is around 5-cm/year
Right before puberty there is a transient phase of poor growth before growth
spurt

Pubertal growth spurt

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Onset of sex hormone production in boys and girls under influence of FSH and
LH
Oestrogen have direct effect at the skeletal growth plate leading to cessation
of growth

Male height chart above

Velocity charts
Around the age of 13-14 there is an increase in cm/years as for the growth spurt
Mid parental height
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Or target height = height of any individual child considered in relation to

height of parents

Growth hormone deficiency should be suspected in patients more than 2.5 SD below
the mean and marked growth failure (height velocity less than 25% percentile for
age). Moderate degrees of short stature with decelerating growth (without reason)
should also suspect growth hormone deficiency.
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Bone age
IGF1 and IGFBP-3
However, majority have normal IGF1 and IGFBP3 (if they are above 50 th
percentile = unlikely to be GHD)
Provactive testing (for those with <10 percentile IGF IGFBP3 and bone age
delay)
o Clonidine, arginine and glucagon (pharmacological stimuli)
o Sleep fasting and exercise (physiological stimuli)
o Hypothyroidism excluded first by performing thyroid function tests.
o None of these tests are gold standards and cause discomfort
Protein stimulates growth factor release thus used for testing

Clonidine Stimulation of GH and GnRH. Can cause hypotension and hypoglycaemia

Arginine no sideeffects
Glucagon transient hyperglycaemia stimulating endogenous insulin and thus GH
secretion. Good choice for infants and children. Side effects;nausea, vomiting,
sweating and headache.

Short stature
Causes
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Genetic (most common)

o Height below 3rd centile
o Growth rate/velocity is NORMAL
o Related to both parents
o Pubertal development occurs at appropriate time
o Bone age is consistent with chronological age
Constitutional delay
o slow growers and late bloomers
o Related to parental late pubertal growth
o Often in boys
Small for gestational age
o Maternal problem
Chronic illness inflammation and malnutrition
o Endocrine problem unlikely to be cause if BOTH weight and height are
affected
o Nutritional insufficiency may contribute to growth failure of chronic
disease
o Anaemia insufficient supply to tissues

o Vit D problem with kidney disease

Skeletal dysplasia
o Achondroplasia
o Hypochondroplasia
o Mucopolysaccaridoses
o Body segment disproportional with increased upper to lower body
segment ratios
o Weight gain is usually normal
Iatrogenic high dose corticosteroids, irradiation to head and spine
Chromosomal abnormality
o Turners
o

Psychosocial
o Abuse and nutritional deficiencies
Endocrine
o Least common
o Hypothyroidism, GH deficiency, Cushing syndrome and adrenal
insufficiency

Uptodate
Treatment of hypopituitarism
Treatment of deficiencies of ACTH, TSH, LH, FSH and GH (unique).
ACTH
TSH

administration of hydrocortisone or other glucocorticoid and timed to mimic

the normal pattern of cortisol secretion. Largest dose in the morning
Larger dose before illness, surgery or procedures
No test to assess the adequacy of replacement
Prednisone and dexamethasone may be preferred due to longer duration of
action
Excessive dose can lead to cortisol excess and bone loss

T4 NOT administered until adrenal function (ACTH reserve) evaluated and

found to be normal or treated.
Hypothyroidism and hypoadrenalism with treatment of hypothyroidism can
increase the clearance of cortisol = severe cortisol deficiency
Weight based T4 dose (as measure of serum TSH not accurate)

LH FSH
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Men = testosterone for those with secondary hypogonadism and no

interested in fertility. Measure serum testosterone
For fertility = GnRH
Women is different oestrogen progesterone replacement therapy

GH
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Recombinant human growth hormone NOT recommended in adults (must

have low IGF1 or poor GH response)

Children with GH
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Biosynthetic growth hormone via subcut.

Starting dose at 20micrograms/kg/day then increasing to 40. Treatment to
start at youngest possible age for best growth response
IGF1 response as dose adjustment (measure 4 weeks post therapy). If low
increase dose if too high can be toxic dose. The goal is to achieve IGF1
slightly higher than average 1 (SD) for mean age.
Growth response should also be monitored target the height velocity 75%
curve or greater than 1SD
Thyroid function also measured incase of hypothyroidism (FT4)
Dosage may need to be increased during puberty (need to achieve expected
height velocity)

Other considrations
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GnRH use in children in early ro mid pubuerty thereby increases adult height
through elaying epiphyseal plate. There are potential risks for this treatment
in reduced bone mineralization, halting puberty effects, cost
Oestrogen blocking effects. Adjunctive therapy to growth hormone.

Adverse effects of recombinant growth hormone

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relatively safe with transient headachhes

Slightly increased risk of idiopathic intracranial hypertension
Increased intraocular pressure
Worsening of scoliosis
Various other rare side effects
Possible increased cancer risk due to higher levels of IGF1 found in those with
breast or prostate cancer (and other cancers)

PBL 2 management
Replacement of hormones

cortisol
Thyroxine
Growth hormone

Surgery for cure

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