By Dr. Zahoor 1

Objectives We will study 1. Pituitary gland and Hypothalamus 2. Increased Secretion of Pituitary Hormone causing disorders 3. Hyposecretion of Pituitary hormones 2

Pituitary gland and Hypothalamus Hypothalamus and anterior pituitary are connected by hypophyseal – pituitary portal blood supply Hypothalamus and posterior pituitary are connected by neural tissue Pituitary gland, size of pea, is enclosed in sella turcica and bridged over by a fold of duramater, has sphenoidal air sinuses below, optic chiasma above, cavernous sinus laterally. Tumor of pituitary can produce visual field defect by pressure on the optic chiasma which lies above the pituitary fossa 3

Hypothalamus - Pituitary Hypothalamic neuron secrete pituitary releasing and inhibiting factors and hormones There are five major anterior pituitary axis - Growth hormone axis - Thyroid axis - Adrenal axis - Gonadotropins axis - Prolactin axis 4

5 Hormones of Anterior and Posterior Pituitary

Hypothalamus - Pituitary Majority of anterior pituitary hormones are under positive control by hypothalamic releasing hormones, except Prolactin which is under tonic inhibition of dopamine Applied – in hypothalamic disease, there is deficiency of anterior pituitary hormones but over secretion of Prolactin 6

Hypothalamus - Pituitary Posterior pituitary is Neuro anatomically connected to hypothalamic nuclei ADH and Oxytocin are synthesized in supraoptic and paraventricular nuclei in anterior hypothalamus They are transported along the axon and stored in posterior pituitary 7

Pituitary Gland Excessive secretion of anterior pituitary causes 1. Acromegly or Gigantism – due to increased growth hormone (GH) 2. Hyperprolactinimia 3. Cushing disease and nelson’s syndrome – due to increased ACTH secretion 8

Pituitary Gland Decreased secretion of anterior pituitary causes 1. Short stature in child due to growth hormone deficiency 2. Hypothyroidism – due to decrease TSH 9

Pituitary Hyper secretion Syndrome Acromegly and Gigantism Increased growth hormone secretion in adults causes Acromegly Increased growth hormone secretion in children (before epiphyseal fusion) causes Gigantism Both Acromegly and Gigantism occur due to pituitary growth hormone secreting tumor 10

Symptoms and Signs of Acromegly 11

12 Symptoms and Signs of Acromegly

Acromegly Investigations GH levels – high in Acromegly (not diagnostic alone as GH increases during stress or GH pulse) Glucose tolerance test (GTT) – it is diagnostic if there is no suppression of growth hormone 13

Acromegly Investigations (cont) IGF – 1 levels are increased Visual field examination – by temporal hemianopia occurs commonly MRI scan of pituitary reveals pituitary adenoma 14

Acromegly Management and Treatment 1. Surgery Pituitary micro adenoma ( size less than 10mm) - Surgery via trans - Sphenoidal route, remission occurs in 60-90% cases Pituitary macro adenoma ( size more than 10mm) - Surgery for large tumors open transcranial usually transfrontal route 15

Acromegly Management and Treatment 2. Radiotherapy External radiotherapy is used when surgery is impracticable or fails to normalize growth hormone (GH )levels 16

Acromegly Management and Treatment (cont) 3. Medical therapy Somatostatin receptor agonist e.g. octreotide.They decrease GH and IGH level Dopamine agonist – Bromocriptine Most effective in mixed GH and Prolactin producing tumor GH antagonist – Pegvisomant- is GH receptor antagonist, it normalizes IGF – 1 level 17

Hyperprolactinaemia Prolactin is secreted by anterior pituitary and is under tonic dopamine inhibition Prolactin stimulates milk secretion from breast Prolactin inhibits gonadal activity and decreases GnRH pulsatility at hypothalamic level Prolactin blocks action of LH on ovary and testis producing hypogonadism 18

19 Control and Action of Prolactin

20 Range of Serum Lactin seen in common causes of Hyperprolactinae mia

Hyperprolactinaemia Physiological causes of Hyperprolactinaemia Pregnancy Lactation Severe stress Sleep 21

Hyperprolactinaemia Pathological causes of Hyperprolactinaemia Prolactinoma (tumor of pituitary gland) Polycystic ovary syndrome Primary hypothyroidism (as TRH increases Prolactin) Rare causes Estrogen therapy Renal failure Liver failure Post-ictal state Chest wall injury 22

Hyperprolactinaemia Drugs causing Hyperprolactinaemia Dopamine antagonist -Metaclopramide -Domperidone -Antipsychotic 23

Hyperprolactinaemia Clinical features Hyperprolactinaemia stimulates milk production in the breast and inhibits GnRH and gonadotropins secretion It usually presents with - Galctorrrhoea - Oligomenorrhoea - Amenorrhoea - Decreased libido in both sexes - Decreased potency in men - Sub fertility - Estrogen or Androgen deficiency (in long term osteoporosis specially in women) - Delayed puberty - Mild gynaecomastia in men 24

Hyperprolactinaemia Investigation Prolactin level – are increased - Mild increase in Prolactin level mU/L may be physiological, level above 5000mU/L always imply Prolactin secreting pituitary tumor Visual field Exclude primary hypothyroidism Radiology for pituitary tumor MRI of pituitary (when Prolactin level above 1000mU/L) 25

Treatment 1. Medical Treatment -Dopamine agonist -Bromocriptine, Carbergoline 2. Trans Sphenoidal surgery 3. Radiotherapy 26

Cushing Disease When there is increased ACTH from pituitary, it is called Cushing Disease Cushing Syndrome Increased Cortisol secretion from adrenal tumor (with suppression of ACTH) Increased free circulating Glucocorticoids due to administration of steroids or ACTH 27

Clinical Presentation Cushing disease - Weight gain - Bruising - Myopathy - Hypertension - Striae - Depression 28

Pseudo Cushing Syndrome Cushingoid appearance can be caused by excess alcohol consumption Treatment for Cushing Disease Trans Sphenoidal removal of tumor Radiotherapy Medical treatment to decrease ACTH - Bromocriptine - Carbergoline 29

Nelson’s Syndrome Increased pigmentation caused by increased ACTH due to enlarging pituitary tumor, which occurs in patients when bilateral adrenalectomy is done 30

Hypopituitarism 31

Hypopituitarism Deficiency of pituitary hormones may be selective or multiple Isolated deficiency of GH, LH/FSH, ACTH or TSH can occur Cause may be genetic and congenital, autoimmune or idiopathic Multiple deficiency can be due to tumor – usually GH and gonadotropins are affected first 32

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Hypopituitarism Clinical features Symptoms and signs depend upon the extent of hypothalamic and/or pituitary deficiencies There may be - GH deficiency - Secondary hypothyroidism - Hypoadrenalism - Gonadal deficiencies - Hyperprolactaenimia - Panhypopituitarism – causes classic picture of pallor with hairlessness (‘alabaster skin’) 34

Syndromes related to Hypopituitarism 35

Syndromes related to Hypopituitarism Kallmann’s Syndrome This syndrome is isolated gonadotropins (GnRH) deficiency There is Anosmia (decreased or absent sense of smell) Color blindness Cleft palate (some times) It is familial, sex linked disorder caused by mutation of KAL1 gene 36

Syndromes related to Hypopituitarism Sheehan’s Syndrome It occurs due to pituitary infarction following postpartum hemorrhage. It is rare in developed countries. Pituitary Apoplexy Sometimes a pituitary tumor enlarges rapidly due to hemorrhage It may produce severe headache, double vision, and sudden visual lose 37

Syndromes related to Hypopituitarism Empty Sella syndrome An (empty Sella) is reported some times on pituitary imaging It may follow spontaneous infarction or regression of pituitary tumor Despite this, pituitary function is usually normal. Why?  Because pituitary is eccentrically placed and flattened against the floor or roof of fossa 38

Posterior Pituitary Vasopressin (ADH) hormone disorder There may be 1. SIADH (Syndrome of Inappropriate ADH secretion) overproduction of ADH 2. Cranial Diabetes Insipidus (due to deficiency of ADH) NOTE – There is nephrogenic Diabetes Insipidus due to resistance effect of V 2 receptors in kidney to hormone ADH 39

Thank you 40