Anterior pituitary gland and disorders its for lectures and students of medical colleges very easy and with diagram and MRI films

1. Dr.prakash shende
MD ( MEDICINE) CCD
CONSULTANT DIABETOGOLIST & CARDIOLOGIST
THYROID SPECIALIST
ASSISTANT PROFESSOR
DR.D Y P H PIMPRI

2. Introduction
 Diseases of the hypothalamus and pituitary are rare,
 Annual incidence is ∼1:50000
 The anterior pituitary is "master gland"
 The anterior pituitary gland produces six major
hormones:
 (1) prolactin (PRL),
 (2) growth hormone (GH),
 (3) adrenocorticotropin hormone (ACTH),
 (4) luteinizing hormone (LH),
 (5) follicle-stimulating hormone (FSH), and
 (6) thyroid-stimulating hormone (TSH)

4. FUNCTIONAL ANATOMY
 The pituitary gland is enclosed in the sella turcica and
bridged over by a fold of dura mater called the
diaphragma sellae, with the sphenoidal air sinuses
below and the optic chiasm above.
 The cavernous sinuses are lateral to the pituitary fossa
and contain the 3rd, 4th and 6th cranial nerves and
the internal carotid arteries.
 The gland is composed of two lobes, anterior and
posterior, and is connected to the hypothalamus by
the infundibular stalk, which has portal vessels
carrying blood from the median eminence of the
hypothalamus to the anterior lobe and nerve fibres to
the posterior lobe.

5. CLASSIFICATION OF DISEASES OF THE PITUITARY
AND HYPOTHALAMUS
 Hormone excess-
Anterior pituitary-
Prolactinoma
Acromegaly
Cushing's disease
Rare TSH-, LH- and FSHomas
 Secondary - Disconnection hyperprolactinaemia
 Hypothalamus and posterior pituitary –
Syndrome of inappropriate antidiuretic hormone

6.  Hormone deficiency –
Anterior pituitary- Hypopituitarism
secondary - e.g. GnRH deficiency (Kallmann's
syndrome)
Hypothalamus and posterior pituitary - Cranial
diabetes insipidus
 Hormone resistance –
Growth hormone resistance (Laron dwarfism)
Nephrogenic diabetes insipidus
 Non-functioning tumours-
Pituitary adenoma
Craniopharyngioma
Metastatic tumours

7. Hypothalamic and Anterior Pituitary Insufficiency
 Hypopituitarism results from impaired production of
one or more of the anterior pituitary trophic
hormones.
 Reduced pituitary function can result from inherited
disorders; more commonly, it is acquired and reflects
the mass effects of tumors or the consequences of
inflammation or vascular damage.

8. Etiology of Hypopituitarism -
 Development/structural
Transcription factor defect
Pituitary dysplasia/aplasia
Congenital CNS mass, encephalocele
Primary empty sella
Congenital hypothalamic disorders (septo-optic dysplasia, Prader-Willi syndrome, Laurence-Moon-Biedl
syndrome, Kallmann syndrome)
 Traumatic
Surgical resection
Radiation damage
Head injuries
 Neoplastic
Pituitary adenoma
Parasellar mass (meningioma, germinoma, ependymoma, glioma)
Rathke's cyst
Craniopharyngioma
Hypothalamic hamartoma, gangliocytoma
Pituitary metastases (breast, lung, colon carcinoma)
Lymphoma and leukemia
Meningioma
 Infiltrative/inflammatory
Lymphocytic hypophysitis
Hemochromatosis
Sarcoidosis
Histiocytosis X
Granulomatous hypophysitis

9.  Infiltrative/inflammatory
Lymphocytic hypophysitis
Hemochromatosis
Sarcoidosis
Histiocytosis X
Granulomatous hypophysitis
 Vascular
Pituitary apoplexy
Pregnancy-related (infarction with diabetes; postpartum
necrosis)
Sickle cell disease
Arteritis
 Infections
Fungal (histoplasmosis)
Parasitic (toxoplasmosis)
Tuberculosis
Pneumocystis carinii

10.  Kallmann Syndrome = Defective hypothalamic
gonadotropin-releasing hormone (GnRH) synthesis &
associated with anosmia or hyposmia due to olfactory bulb
agenesis or hypoplasia
 The syndrome may also be associated with color blindness,
optic atrophy, nerve deafness, cleft palate, renal
abnormalities, cryptorchidism, and neurologic
abnormalities such as mirror movements.
 Defects in the KAL gene, which maps to chromosome
Xp22.3
 Bardet-Biedl Syndrome- rare genetically heterogeneous
disorder characterized by mental retardation, renal
abnormalities, obesity, and hexadactyly, brachydactyly, or
syndactyly.
 Central diabetes insipidus may or may not be associated.
GnRH deficiency occurs in 75% of males and half of
affected females.

11.  Acquired Hypopituitarism =
 Pituitary Apoplexy-
 Acute intrapituitary hemorrhagic
 Damage to the pituitary and surrounding sellar structures.
 Its occur spontaneously in a preexisting adenoma; post-partum (Sheehan's
syndrome); or in association with diabetes, hypertension, sickle cell anemia, or
acute shock.
 The hyperplastic enlargement of the pituitary during pregnancy increases the
risk for hemorrhage and infarction.
 It is an endocrine emergency that may result in severe hypoglycemia,
hypotension, central nervous system (CNS) hemorrhage, and death.
 Acute symptoms may include severe headache with signs of meningeal
irritation, bilateral visual changes, ophthalmoplegia, and, in severe cases,
cardiovascular collapse and loss of consciousness.
 Pituitary computed tomography (CT) or MRI may reveal signs of intratumoral
or sellar hemorrhage, with deviation of the pituitary stalk and compression of
pituitary tissue.
 Patients with no evident visual loss or impaired consciousness can be observed
and managed conservatively with high-dose glucocorticoids.
 Those with significant or progressive visual loss or loss of consciousness require
urgent surgical decompression.
 Visual recovery after surgery is inversely correlated with the length of time after
the acute event. Therefore, severe ophthalmoplegia or visual deficits are
indications for early surgery. Hypopituitarism is very common after apoplexy.

12.  Empty Sella-
 A partial or apparently totally empty sella is often an
incidental MRI finding.
 These patients usually have normal pituitary function,
implying that the surrounding rim of pituitary tissue is
fully functional.
 Hypopituitarism, however, may develop insidiously.
 Rarely, small but functional pituitary adenomas may
arise within the rim of pituitary tissue, and these are
not always visible on MRI

13. Tests of Pituitary Sufficiency
 Growth hormone –
Test- Insulin tolerance test:
Blood Samples- Regular insulin (0.05–0.15 U/kg IV) –
30, 0, 30, 60, 120 min for glucose and GH
Interpretation- Glucose < 40 mg/dL;
GH should be >3 g/L,
 Prolactin –
TRH test: 200–500 g IV
Blood Samples- 0, 20, and 60 min for TSH and PRL
Interpretation- Normal prolactin is >2 g/L and increase >200% of
baseline
 ACTH-Test-
Standard ACTH stimulation test: ACTH 1-24 (Cosyntropin),
0.25 sa mg IM or IV m
Blood sample - 0, 30, 60 min for cortisol and aldosterone
Interpretation- Normal response is cortisol >21 g/dL and
dosterone response of >4 ng/dL above baseline

14.  TSH
Test- Basal thyroid function tests: T4, T3, TS
sample- Basal tests
Interpretation- Low free thyroid hormone levels in the
setting of TSH levels that are not appropriately
increased

15. Hypopituitarism: Treatment
 ACTH-Hydrocortisone
(10–20 mg A.M.; 5–10 mg P.M.)
Cortisone acetate (25 mg A.M.; 12.5 mg P.M.)
Prednisone (5 mg A.M.; 2.5 mg P.M.)
 TSH L-Thyroxine (0.075–0.15 mg daily)
 FSH/LH male
Testosterone enanthate (200 mg IM every 2 weeks)
Testosterone skin patch (5 mg/d)
Females
Conjugated estrogen (0.65–1.25 mg qd for 25 days)
Progesterone (5–10 mg qd) on days 16–25
Estradiol skin patch (0.5 mg, every other day)
For fertility: Menopausal gonadotropins, human chorionic
gonadotropins
GH Adults: - Somatotropin (0.1–1.25 mg SC qd)
Children: Somatotropin [0.02–0.05 (mg/kg per day)]
Vasopressin- Intranasal desmopressin (5–20 g twice daily)
Oral 300–600 g qd

16. PITUITARY AND (PARA-)SELLAR TUMOURS
 Lesion may simply be an incidental discovery during
neuroimaging for another indication (e.g. the investigation
of cerebrovascular disease).
 Sellar and para-sellar tumours produce a variety of mass
effects, depending on their size and location.
 The most common is headache, which is due to
stretching of the diaphragma sellae.
 Compression of the neural connections between the retina
and occipital cortex may lead to a visual field defect. –
bitemporal hemianopia or upper quadrantanopia, any
type of visual field defect can result from suprasellar
extension of a tumour because of compression of the optic
nerve (unilateral loss of acuity or scotoma) or the optic
tract (homonymous hemianopia).
 Lateral extension into the cavernous sinus with
subsequent compression of the 3rd, 4th or 6th cranial
nerves may cause diplopia and strabismus.

18. Aetiology and investigations-
 Majority of intrasellar tumours are pituitary
macroadenomas (most commonly non-functioning
adenomas, ) most suprasellar masses are
craniopharyngiomas , and para-sellar masses are most
commonly meningiomas.
 Diagnosis requires surgical biopsy.
 All patients with (para-)sellar space-occupying lesions
should have pituitary function test

19. Management
 If there is evidence of pressure on visual pathways, then
urgent treatment is required.
 The chances of recovery of a visual field defect are
proportional to the duration of symptoms; full recovery
is unlikely if the defect has been present for longer than
4 months.
 Serum prolactin is measured before emergency surgery
is performed.
 If the prolactin is > 5000 mU/l, then the lesion may be a
macroprolactinoma and a therapeutic trial of a
dopamine agonist for just a few days may successfully
shrink the lesion and make surgery unnecessary

20. Surgery
Radiot
herapy Medical Comment
Non-functioning
pituitary macroadenoma
1st line 2nd line -
Prolactinoma 2nd line 2nd line 1st line
Dopamine agonists
Dopamine agonists
usually cause
macroadenomas to
shrink
Acromegaly 1st line 2nd line 2nd line
Somatostatin analogues
Dopamine agonists
GH receptor antagonists
Medical therapy does not
reliably cause
macroadenomas to
shrink
Cushing's disease 1st line 2nd line - Radiotherapy is used in
children and to prevent
Nelson's syndrome
Craniopharyngioma 1st line 2nd line

21.  Most operations on the pituitary are performed by the
trans-sphenoidal approach.
 The pituitary fossa is approached via the sphenoid
sinus from an incision under the upper lip or through
the nose.
 Transfrontal surgery via a craniotomy is reserved for
suprasellar tumours.
 Pituitary function should be retested 4-6 weeks
following surgery.

22. HYPERPROLACTINAEMIA-
 Hyperprolactinaemia is a common biochemical
abnormality.
 The cardinal features are galactorrhoea and
hypogonadism.
 Galactorrhoea describes lactation without
breastfeeding.
 Prolactin stimulates milk secretion but not breast
development, so that galactorrhoea almost never
occurs in men.

23. HYPERPROLACTINAEMIA
 Physiological Stress (e.g. post-seizure)
 Pregnancy
 Lactation
 Nipple stimulation
 Sleep
 Coitus
 Exercise
 Baby crying
 Drugs Dopamine antagonists Antipsychotics (phenothiazines and butyrophenones)
 Antidepressants
 Antiemetics (e.g. metoclopramide, domperidone)
 Dopamine-depleting drugs Reserpine
 Methyldopa
 Oestrogens Oral contraceptive pill
 Pathological Common Disconnection hyperprolactinaemia (e.g. non-functioning
pituitary macroadenoma)
 Prolactinoma (usually microadenoma)
 Primary hypothyroidism
 Polycystic ovarian syndrome
 Macroprolactinaemia
 Uncommon Hypothalamic disease
 Pituitary tumour secreting prolactin and growth hormone
 Renal failure

24.  Prolactinoma - Most prolactinomas in pre-menopausal
women are microadenomas.
 In men and post-menopausal women, presentation is
often much more insidious and the tumours are almost
invariably macroadenomas at the time of diagnosis.
 Macroprolactin (or 'big, big prolactin') is prolactin
bound to an IgG antibody.
 Many prolactin assays do not distinguish
macroprolactin from monomeric (i.e. unbound)
prolactin.
 Identification requires gel filtration chromatography or
polyethylene glycol precipitation techniques.
 Macroprolactin cannot cross blood vessel walls to reach
prolactin receptors in target tissues and so is less likely
to cause the classical symptoms of hyperprolactinaemia.

25.  Presentation and Diagnosis-
 Amenorrhea, galactorrhea, and infertility are the hallmarks
of hyperprolactinemia in women.
 If hyperprolactinemia is sustained, vertebral bone mineral
density can be reduced.
 Patients may also complain of decreased libido, weight
gain, and mild hirsutism.
 In men with hyperprolactinemia, diminished libido,
infertility, or visual loss (from optic nerve compression) are
the usual presenting symptoms.
 Gonadotropin suppression leads to reduced testosterone,
impotence, and oligospermia..
 The diagnosis of idiopathic hyperprolactinemia is made by
exclusion of known causes of hyperprolactinemia in the
setting of a normal pituitary MRI.
 Some of these patients may harbor small microadenomas
below MRI sensitivity (~2 mm).

26.  Investigations -.
 Pregnancy should be excluded in all women of child-bearing potential.
 The upper limit of serum prolactin is ∼500 mU/l (∼14 ng/ml).
 In non-pregnant and non-lactating patients, monomeric prolactin
concentrations of 500-1000 mU/l are likely to be induced by stress or
drugs, and a repeat measurement is indicated.
 Levels between 1000 and 5000 mU/l are likely to be due to either
drugs, a microprolactinoma or 'disconnection' hyperprolactinaemia.
 Levels above 5000 mU/l are highly suggestive of a macroprolactinoma,
and the higher the level, the bigger the tumour.
 Some macroprolactinomas cause levels over 100 000 mU/l.
 Patients with prolactin excess should have tests of gonadal function
and T4 and TSH measured to exclude primary hypothyroidism causing
TRH-induced prolactin excess.
 Unless the prolactin falls after withdrawal of relevant drug therapy, a
serum prolactin of > 1000 mU/l is an indication for MRI or CT scan of
the hypothalamus and pituitary.
 Patients with a macroadenoma also need tests for hypopituitarism

27. Management
 Medical -Medical Dopamine agonist drugs are first-line
therapy .
 In patients with macroadenomas, drugs can only be
withdrawn after curative surgery or radiotherapy and
under close supervision.
 DOPAMINE AGONIST THERAPY: DRUGS USED TO
TREAT PROLACTINOMAS-
 Bromocriptine 2.5-15 mg/day
8-12-hourly
 Available for parenteral use
Short half-life; useful in treating infertility
Proven long-term efficacy Ergotamine-like side-effects
(nausea, headache, postural hypotension,
constipation)

28.  Cabergoline 250-1000 μg/week
2 doses/week Long-acting
Reported to have fewer ergotamine-like side-effects Limited data
on safety in pregnancy
Quinagolide 50-150 μg/day
Once daily
A non-ergot with few side-effects
Untested in pregnancy
 Surgical - Dopamine agonists not only lower prolactin levels, but
shrink the majority of prolactin-secreting macroadenomas.
Thus, surgical decompression is not usually necessary unless the
macroadenoma is cystic.
However, in patients who are intolerant of dopamine agonists,
microadenomas can be removed selectively by trans-sphenoidal
surgery with a cure rate of about 80%.
The cure rate for surgery in macroadenomas is lower.
 Radiotherapy- External irradiation may be required for some
macroadenomas to prevent regrowth if dopamine agonists are
stopped