Endo 1.07 The pituitary gland

• Anatomy and histology of the pituitary gland

• Growth hormone and its control

• Actions of growth hormone

• Excess and deficiency of GH

• Causes of pituitary failure

• Micro- and macroadenomas

• Prolactin and prolactinomas

• Arginine vasopressin and its control

• Actions of AVP

• Diabetes insipidus

Embryology of the pituitary gland

Pituitary in pocket of sphenoid bone

Reflection of dura mater allows the entire gland to be surrounded by dura

Thus the arachnoid membrane and CSF cannot enter the sella turcica

Anterior pituitary cells and their hormones

Chromophobes

Cell type

Chromophils

Acidophils Basophils

Growth hormone TSH, ACTH Prolactin LH & FSH

Histology of the pituitary gland

ACTH secreting cells

PRL secreting cells

Immunohistochemical identification of cells

secreting specific adenohypophyseal

hormones

HORMONE SECRETIONS OF THE ANTERIOR PITUITARY GLAND

Hormone % Pituitary cell population

TSH * 3-5%

ACTH * 15-20%

LH/FSH * 10-15%

GH # 40-50%

Prolactin # 10-15%

* Basophil # Acidophil

Growth hormone and prolacin

Actions of growth hormone

MAJOR FACTORS CONTROLLING MAJOR FACTORS CONTROLLING GROWTH HORMONE SECRETIONGROWTH HORMONE SECRETION

STIMULATION INHIBITIONGHRH Somatostatin

Hypoglycaemia Hyperglycaemia

Decreased fatty acids Increased fatty acids

Starvation IGF’s

Exercise/sleep Growth hormone

Stress

Androgens, estrogens Progesterone

-adrenergic agonists -adrenergic

Serotonin Serotonin antagonists

Dopamine agonists Dopamine antagonists

Symptoms of GH deficiencySymptoms of GH deficiency

•Decreased energy levels

•Social isolation

•Lack of positive well being

•Depressed mood

•Increased anxiety

Clinical features of GH Clinical features of GH deficiencydeficiency

• Increased body fat

• Decreased muscle mass

• Decreased bone density

• Increased LDL and decreased HDL cholesterol

• Decreased insulin sensitivity

• Decreased total fluid volume

Insulin induced hypoglycaemia to test for GH deficiency

Treatment of poor growth

• Growth hormone

• Growth hormone releasing hormone

• IGF (growth hormone insensitivity)

• Oxandrolone

Acromegaly

Clinical features of acromegaly

Symptoms

• Carpal tunnel syndrome

• Arthralgia/arthritis

• Excessive sweating

• Angina

• Diurnal drowsiness

• Polydipsia, polyuria

• Renal colic

• Menstrual irregularities

• Impotence

Signs

• Enlarged hands and feet, jaw protusion

• Osteoarthritis

• Greasy skin

• Hypertension

• Cardiomyopathy

• Obstructive sleep apnoea

• Retinopathy, neuropathy

• Renal stones

• Hypogonadism

Oral glucose load to test for GH excess

Causes of pituitary failureDevelopmental abnormalities

Trauma

• Inflammation - viral bacterial or fungal infections

• Infiltrative disease e.g. sarcoidosis

• Tumours of the brain or hypothalamus

• Radiation

• Tumours of the pituitary gland

Pituitary adenomas

Classified by size and hormones they produce

Microadenomas < 1cm diameter

Macroadenomas > 1 cm

30% prolactinomas

15% GH hypersecretion

10% ACTH secreting

10% gonadotrophinomas

< 1% TSH secreting

30% null cell (no hormone)

Chromophobic adenoma

Macroadenomas• Sellar enlargement

• suprasellar damage

• visual loss

• hypopituitarism

• extension into cavernous sinuses

Microadenomas• Tend to present with symptoms of hormonal excess

Treatment of pituitary adenomasTreatment of pituitary adenomas

• Medical

Dopamine agonists e.g. carbergoline/bromocryptine

GH analogue e.g. octreotide

GH receptor antagonists e.g. pegvisomant

• Surgical - transphenoidal surgery • Radiotherapy

Saggital MR scans of a) normal and b) a patient with a craniopharyngioma causing bitemporal hemianopia and

hypopituitarism

including

TRH

Control of prolactin secretion

Causes of Causes of hyperprolactinaemiahyperprolactinaemia

Common ~ 90%

• Dopamine D2 receptor antagonists (antiemetics/neurolepetics)

• Primary hypothyroidism (TRH)

Uncommon ~ 10%

• Pituitary tumour

• ‘Stalk syndrome’ (loss of dopamine)• Macroprolactinaemia (Immunoglobulin binds to

prolactin)

Coronal scans of a patient with a prolactinoma before and after

treatment with cabergoline

Synthesis of arginine

vasopressin and

oxytocin

Actions and control of vasopressin

Increase of vasopressin secretion in response to:

a) % increase in blood volume depletion

b) Increasing plasma osmolality

DIABETES INSIPIDUS

• CENTRAL - Impaired VP synthesis

• NEPHROGENIC - Resistance to VP

Lithium

CLINICAL TEST - 8h water deprivation/

saline load

SYMPTOMS - Polyuria/thirst

Tests for central and nephrogenic diabetes

insipidus

Changes in plasma osmolality (A) and urine osmolality (B) after 8 hours water deprivation and after an intramuscular injection of a long-acting synthetic vasopressin analogue, desmopressin

AVP response to an infusion of 3-5% sodium chloride