Pituitary Disorders By Dr. Zahoor

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

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.

Pituitary gland and Hypothalamus Tumor of pituitary can produce visual field defect by pressure on the optic chiasma which lies above the pituitary fossa

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

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

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

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

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

Pituitary Hyper secretion Syndrome - Acromegly - 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

Symptoms and Signs of Acromegly

Symptoms and Signs of Acromegly

Symptoms and Signs of Acromegly Compare hands Ring Finger

Acromegly Investigations GH levels – high in Acromegly (not diagnostic alone as GH increases during stress or GH pulse) Growth hormone suppression test- Glucose tolerance test (GTT) and GH levels – it is diagnostic if there is no suppression of growth hormone after glucose load IGF – 1 levels are increased

Acromegly Investigations (cont) Visual field examination – by temporal hemianopia occurs commonly MRI scan of pituitary reveals pituitary adenoma

Acromegly Management and Treatment 1. Surgery Pituitary micro adenoma - Surgery via trans - Sphenoidal route, remission occurs in 60-90% cases Pituitary macro adenoma - Surgery for large tumors open transcranial usually transfrontal route

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

Acromegly Management and Treatment 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 receptor antagonist – Pegvisomant (Somavert) is GH receptor antagonist, by blocking the action of GH , it controls disease activity.

Hyperprolactinaemia

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

Control and Action of Prolactin

Range of Serum Prolactin seen in common causes of Hyperprolactinaemia

Hyperprolactinaemia Physiological causes of Hyperprolactinaemia Pregnancy Lactation Severe stress Sleep

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

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

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

Hyperprolactinaemia Clinical features (cont) - Estrogen or Androgen deficiency (in long term osteoporosis specially in women) - Delayed puberty - Mild gynaecomastia in men

Hyperprolactinaemia Investigation Prolactin level – are increased - Mild increase in Prolactin level 400-600mU/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)

Treatment Medical Treatment -Dopamine agonist -Bromocriptine, Carbergoline Trans Sphenoidal surgery Radiotherapy

Hypopituitarism

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

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’)

Syndromes related to Hypopituitarism

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

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

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 of roof of fossa

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 V2 receptors in kidney to hormone ADH

Case History A 50 year old woman is referred to the hospital with history of sweating and joint pains. She has 10 year history of hypertension and more recently has been discovered to have impaired glucose tolerance. The striking feature on examination is her deep voice and oily skin. A medical student notices increase inter-dental space and macroglossia, and suggests a possible diagnosis of Acromegly. Further questioning elicits increased shoe size, and the need to enlarge her wedding ring 3 times over the last 15 years.

Questions: What test would be more helpful in the diagnosis? a. Growth hormone b. Oral glucose tolerance test (OGTT) c. OGTT and growth hormone combined d. Calcium What further investigation should be performed? a. Dexamethasone test b. Inferior petrosal sinus sampling c. MRI of Pituitary d. None Best treatment choice in Acromegly is a. Somatostatin receptor agonist b. Dopamine agonist c. Radiotherapy alone d. Pituitary surgery

Answers: Answer to Question 1: c. OGTT and growth hormone combined Answer to Question 2: c. MRI of Pituitary Answer to Question 3: d. Pituitary Surgery

Thank you