Pituitary Adenomas

Classified based on the basis of hormones produced + whether they are

functional (associated with hormonal excess) or non-functioning
(without clinical symptoms of hormone excess)
Non-functional adenomas typically are larger at the time of diagnosis due
to the lack of clinical syndromes associated with hormone release
Peak incidence from 35-60 years of age
Microadenomas < 1cm in diameter
Macroadenoma > 1cm in diameter

Pituitary Cell type

Hormone

Tumor Type

Corticotroph

ACTH cell
adenoma

Somatotroph

ACTH and other

POMC derived
peptides
GH

Lactotroph

Prolactin

Prolactin cell
adenoma

Mammosomatotro
ph

Prolactin + GH

Mammosomatotro
ph

Thyrotroph
Gonadotroph

TSH
FSH + LH

TSH cell adenoma

Gonadotroph null
cell oncocytic
adenomas

GH cell adenoma

Associated
Syndrome
Cushing syndrome
+ Nelson
syndrome
Gigantism
(children)/
Acromegally
(adults)
Galactorrhea and
amenorrhea
(females), sexual
dysfunction,
infertility
Combined GH and
prolactin
symptoms
Hyperthyroidism
Hypogonadism,
mass effects and
hypopituitarism

G-protein mutations are common in pituitary tumours

95% of adenomas are sporadic in nature (5% arise from an inherited
predisposition)
As many as 30% of adenomas are not grossly encapsulated and can
infiltrate the cavernous and sphenoid sinuses, dura and occasionally the
brain itself
Cavernous sinus contains III, IV and VI cranial nerves so nerve lesions may
occur with invasion
Headache can arise from the bony structures or meninges
Mass effect on the hypothalamus altered appetite, obesity, thirst,
somnolence/wakefulness or precocious puberty
Sphenoid sinus invasion can cause CSF rhinorrhoea
Generalised signs: radiographic abnormalities, visual field abnormalities,
raised intra-cranial pressure and occasionally hypopituitarism

Prolactinomas

Most frequent type of hyperfunctioning pituitary adenoma (30% of cases)

Proportionally the serum prolactin concentrations tend to correlate with
the size of the adenoma
Increased serum levels of prolactin amenorrhea, galactorrhea, loss of
libido and infertility
Diagnosis is made more readily in women due to the disruption of menses
Prolactinoma underlies almost 25% of cases of amenorrhoea
In men and older women diagnosis may be more difficult
Physiologic hyperprolactinaemia occurs in pregnancy and during breast
feeding; pathologic HP also results from lactotroph hyperplasia
(abnormality in dopaminergic inhibition); any mass in in the suprasellar
compartment disturbs pituitary secretion therefore prolactin may be
slightly increased in other tumours

GH Cell Adenomas

Second most common type

Children gigantism generalised increase in body size with
disproportionately long asms and legs
Post-epiphyseal plate closure acromegaly growth in skin, soft tissues,
viscera (thyroid, heart, liver and adrenals), and bones of the face, hands
and feet protrusion of the jaw (prognathism), broadening of the lower
face, enlarged hands and feet
Also associated with gonadal dysfunction, diabetes mellitus, generalised
muscle weakness, hypertension, arthritis, CCF, and increased risk of
gastrointestinal cancers

ACTH Cell Adenomas

Hypercortisolism Cushing syndrome

Large destructive adenomas can develop in patients after surgical removal
of the adrenals (for treatment of Cushings) due to the loss of the
inhibitory function of adrenal corticosteroids = Nelson syndrome

Investigations

MRI
Visual fields
Hormone serology

Acromegaly

A rare, potentially life-threatening condition that involves increased and

unregulated growth hormone (GH) production, usually caused by a GHsecreting pituitary tumour (somatotroph tumour)

Epidemiology

1 in 3-4 million people

Mean age of 40-45 years
Mortality rate is twice that of normal population
Have increased risk of cardiorespiratory, cerebrovascular diseases,
diabetes and neoplasis, esp colon cancer
Occurs with equal frequency in males and females

Pathophysiology

More than 95% of cases caused by pituitary adenoma that secretes excess
amounts of GH
5% caused by:
o increased GHRH (GH releasing hormone) from hypothalamic
tumours
o ectopic GHRH from non-endocrine tumours
o ectopic GH secretion by non-endocrine tumours
Pathologic effects of excess GH
o Acral overgrowth
macrognathia; enlargement of the facial bone structure;
enlarged hands and feet; visceral overgrowth, including
macroglossia and enlarged heart muscle, thyroid, liver,
kidney
o Insulin antagonism
o Nitrogen retention
o Increased risk of colon polyps/tumours

Clinical Features

Acromegaly can be an insidious disease. Symptoms might precede

diagnosis by several years.
Symptoms can be divided into 2 groups:
o Symptoms due to local mass effects of the tumourSymptoms
depend on the size of the intracranial tumour
Headaches and visual field defects are the most common
symptoms.
Visual field defects depend on which part of the optic
nerve pathway is compressed.

Bitemporal hemianopsia due to pressure on the optic

chiasm.
Hyperprolactinemia dueto tumor damage to the pituitary
stalk which cause loss of inhibitory regulation of prolactin
secretion by the hypothalamus.
Damage to normal pituitary tissue can cause deficiencies
of glucocorticoids, sex steroids, and thyroid hormone.
Loss of end organ hormones is due to diminished anterior
pituitary secretion of corticotropin (ie, adrenocorticotropic
hormone [ACTH]), gonadotropins (eg, luteinizing hormone
[LH], follicle-stimulating hormone [FSH]), and thyrotropin (ie,
thyroid-stimulating hormone [TSH]).
Symptoms due to excess of GH/IGF-I
Soft tissue swelling and enlargement of extremities
Increase in ring and/or shoe size
Hyperhidrosis
Coarsening of facial features
Frontal bossing
Nose thickening
Macroglossia (tongue hypertrophy)
Prognathism (abnormal protrusion of mandible)
Arthritis
Increased incidence of obstructive sleep apnea
Increased incidence of glucose intolerance or frank diabetes
mellitus, hypertension, and cardiovascular disease
Hyperphosphatemia, hypercalcuria, and hypertriglyceridemia
possible
Increased incidence of congestive heart failure, which might
be due to uncontrolled hypertension or to an intrinsic form of
cardiomyopathy attributable to excess GH/IGF-I
Increased incidence of colonic polyps and adenocarcinoma of
the colon

Investigations

Because GH secretion is inhibited by glucose, measurement of glucose

nonsuppressibility might be useful. Two baseline GH levels are obtained
prior to ingestion of 75 or 100 g of oral glucose, and additional GH
measurements are made at 30, 60, 90, and 120 minutes following the oral
glucose load.
CT scan of the abdomen/pelvis evaluates for pancreatic, adrenal, or
ovarian tumors secreting GH/GHRH. Chest CT scanning evaluates for
bronchogenic carcinoma secreting GH/GHRH.

Management

Surgery as the first line of treatment, followed by medical therapy for

residual disease

Su
rg
er
y:

Transsphenoidal hypophysectomy has the dual advantage of rapidly

improving symptoms caused by mass effect of the tumor and
significantly reducing or normalizing GH/IGF-I concentrations
Medical: Somatostatin and dopamine analogues and GH receptor
antagonists are the mainstays of medical treatment and are
generally used after failure of primary surgery to induce complete
remission

Diabetes Insipidus
Definition and Pathophysiology

A disorder that causes the patient to produce tremendous quantities of

dilute urine. The massively increased urine output is usually accompanied
by intense thirst.
Central/cranial DI :
o Due to decreased secretion of antidiuretic hormone (ADH)
by hypothalamusalso known as arginine vasopressin (AVP)
which gives rise to polyuria and polydipsia by diminishing the
patients ability to concentrate urine.
Result of a defect in 1 or more sites involving the
hypothalamic osmoreceptors, the supraoptic or
paraventricular nuclei, or the supraopticohypophyseal tract.
Nephrogenic DI
o Decrease in the ability to concentrate urine due to
unresponsiveness of renal tubules to ADH. Nephrogenic DI can
be observed in chronic renal insufficiency, lithium toxicity,
hypercalcemia, hypokalemia, and tubulointerstitial disease; rarely,
diabetes insipidus may be hereditary.

Epidemiology

Uncommon in the United States, with a prevalence of 1 case per 25,000

population.
No significant sex differences in central or nephrogenic diabetes
insipidus exist: male and female prevalences are equal.
The prognosis is generally excellent, depending upon the underlying
illness.
Mortality is rare in adults as long as water is available.
Complication:
o Severe dehydration, hypernatremia, fever, cardiovascular collapse,
and death can ensue in children, elderly people, or in those with
complicating illnesses.

Etiology

30% of DI cases are idiopathic, 25% are related to malignant or

benign tumors of the brain or pituitary, 20% follow cranial surgery,
and 16% are secondary to head trauma.
Genetic: autosomal dominant
Idiopathic DI destruction of cells in the hypothalamus, often as part of
an autoimmune process
Structural hypothalamic or high stalk lesion
o Primary or secondary tumours, cyst, haemorrhage

The most common causes of postoperative polyuria are excretion of

excess fluid administered during surgery and an osmotic diuresis
resulting from treatment for cerebral edema.
Metabolic abnormality: hypokalaemia, hypercalcaemia
Chronic kidney disease: polycystic kidney disease, etc

Differential Diagnosis

Diabetes mellitus
Primary polydipsia (often seen in psychiatric pt)

Clinical Features

The clinical presentation of diabetes insipidus (DI) depends on the cause,

the severity, and the associated medical condition(s) of the patient.
o History
Polyuria, polydipsia, and nocturia (from 3-18 L) are the
predominant symptoms.
o urine is of low specific gravity and osmolality
o if pt is conscious -> can maintain adequate fluid intake
o if pt is unconscious -> DI is lethal
In infants, crying, irritability, growth retardation,
hyperthermia, and weight loss may be the most apparent
signs.
In children, enuresis, anorexia, linear growth defects, and
fatigability typically predominate.
Pregnancy is associated with an increased risk of DI.
Many patients have a predilection for drinking cold liquids,
often water. Neurologic symptoms vary with the patients
access to water; patients with free access may have no
symptoms at all.
o Physical Examination
Varies with the severity and chronicity of DI.
The examination findings may be entirely normal.
Hydronephrosis, bladder enlargement, and signs of
dehydration are common.

Investigations

Water deprivation testing

o Use: to establish diagnosis of DI and differentiate cranial and
nephrogenic causes
o Measure plasma osmolality and urine osmolality hourly after water
intake is withheld

DI is confirmed if plasma osmolality is elevated

(>300mOsm/kg, normal is 275-299) with a urine osmolality is
<600 mOsm/kg (normal is >850)
If healthy: water deprivation leads to urine osmolality
that is 2-4 times greater than plasma osmolality
Cranial DI: if urine osmolality arises by at least after
admisitration of exogenous ADH
Nephrogenic: kidney fails to respond to exogenous ADH to
concentrate the urine

Management

DDAVP (des-amino-des-aspartate-arginine vasopressin desmospressin

o An ADH analogue -> to reliev inadequate thirst in central DI
Polyuria in nephrogenic insipidus is improved by thiazide diuretics,
amiloride and NSAIDs

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Definition

The hyponatremia and hypo-osmolality resulting from inappropriate,

contined secretion or action of the hormone despite normal or increased
plasma volume, which results in impaired water excretion

Pathophysiology

Nonphysiological secretion of ADH results in enhanced water absorption,

leading to dilutional hyponatremia and volume expansion
Volume receptors are activated and natriuretic peptides are secreted,
which causes natriuresis and some degree of accompanying potassium
secretion.
Eventually, a steady state is reached and the amount of Na + excreted in
the urine matches Na+ intake
Ingestion of water is an important factor to the development of the
syndrome; regardless of cause, hyponatremia does not occur if water
intake is severely restricted

Etiology

Most often caused by either inappropriate hypersecretion of ADH from its

normal hypothalamic source or by ectopic production
Can be divided into 4 broad categories:
o Nervous system disorders
o Neoplasia
o Pulmonary diseases
o Drug induced (which include those that [1] stimulate AVP release,
[2] potentiate effects of AVP action, or [3] have an uncertain
mechanism)

Clinical Features

In general, slowly progressive hyponatremia is associated with fewer

symptoms than is a rapid drop of serum Na + to the same value
Some patients with profound hyponatremia may be relatively
asymptomatic. Anorexia, nausea, and malaise are early symptoms and
may be seen when the serum Na+ level is less than 125 mEq/L. A further
decrease in the serum Na+ level can lead to headache, muscle cramps,
irritability, drowsiness, confusion, weakness, seizures, and coma

Investigations

Laboratory testing:
o Electrolytes (low Na+ level)
o Creatinine
o Blood urea nitrogen
o Uric acid (usually low)
o TSH (to rule out hypothyroidism)
o 8 am cortisol (to rule out adrenal insufficiency)
o Urinalysis: increased osmolarity