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 GROWTH HORMONE SECRETION STIMULATIONINHIBITION GHRHSomatostatin HypoglycaemiaHyperglycaemia Decreased fatty acidsIncreased fatty acids StarvationIGF’s Exercise/sleepGrowth hormone Stress Androgens, estrogensProgesterone  -adrenergic agonists  -adrenergic SerotoninSerotonin antagonists Dopamine agonistsDopamine antagonists

Symptoms of GH deficiency Decreased energy levels Social isolation Lack of positive well being Depressed mood Increased anxiety

Clinical features of GH deficiency 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 failure Developmental 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 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 hyperprolactinaemia 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