1. Pituitary Disorders
By Dr. Zahoor

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

3. 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.

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

5. 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

6. Hormones of Anterior and Posterior Pituitary

7. 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

8. 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

9. 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

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

11. 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

12. Symptoms and Signs of Acromegly

13. Symptoms and Signs of Acromegly

14. Symptoms and Signs of Acromegly
Compare hands
Ring Finger

15. 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

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

17. 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

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

19. 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.

20. Hyperprolactinaemia

21. 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

22. Control and Action of Prolactin

23. Range of Serum Prolactin seen in common causes of Hyperprolactinaemia

24. Hyperprolactinaemia Physiological causes of Hyperprolactinaemia
Pregnancy
Lactation
Severe stress
Sleep

25. 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

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

27. 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

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

29. 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)

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

31. Hypopituitarism

32. 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

34. 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’)

35. Syndromes related to Hypopituitarism

36. 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

37. 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

38. 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

39. 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

40. 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.

41. 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

42. 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

43. Thank you