Pituitary Disorders

Question 1

This deck covers

Answer 1

Hypersecretion disorders:

• Cushing’s Disease
• Hyperprolactinaemia
• Acromegaly

Hyposecretion disorders:

• Craniopharyngioma
• Infection
• Sheehan’s syndrome
• Cranial Diabetes Insipidus

Question 2

What is Acromegaly?

Answer 2

• Excess production of Growth Hormone after the long bones fuse (i.e. in adults)
• Before long bones fuse is gigantism.
• In acromegaly there is excess growth hormone secondary to a pituitary adenoma in over 95% of cases.

Question 3

How does acromegaly present?
Symptoms [7]
Signs [6]

Answer 3

Symptoms

• Rings and shoes no longer fitting
• Headaches
• Wonky bite
• Sweating, snoring (OSAS)
• Amenorrhea, reduced libido
• Galactorrhea
• Paresthesia

Signs

• Coarse facial features
• Increased growth of hands, jaw, feet
• Macroglossia, puffy lips, eyelids
• Scalp folds, skin darkening, acanthosis
• Goitre
• CTS

Remember features of a pituitary tumour: hypopituiraism, headaches, bitemporal hemianopia

Question 4

What complications can arise from excess GH? [5]

What kind of follow up is required post-treatment of acromegaly? [5]

Answer 4

• Chiasmal Compression
• DM, Hypertension
• Cardiomyopathy
• Accelerated Osteoarthritis
• Colonic Polyps & adenoma > CRC

Follow up:

• Annual GH and IGF-1
• OGTT
• Visual field and vascular assessment
• BMI
• Photos

Question 5

How would you test someone for Acromegaly? [4]

Treatment options [3]

Answer 5

1. Visual Field Testing (chiasmal compression –> Bitemporal Hemianopia)
2. Screen potential patients for IGF-1 Elevation - also used in monitoring of patients
3. Confirm diagnosis with an OGTT if IGF-1 unequivocal. Acormegaly is diagnosed with GH suppressed.
4. MRI for pituitary tumour

Treatment

• Transphenoidal resection
• Somatostatin analogues OCTREOTIDE monthly IM (inhibits GH)
• GH receptor antagonist PEGVISOMANT, OD S/C.
• Bromocriptine has been superceded.
• External irradiation following failed surgical/medical tx in older patients.

Question 6

What is Cushing’s Disease? [2]

Answer 6

Excessive Glucocorticoids [1] due to the excessive ACTH [1] release from pituitary

Question 7

Presentation Cushing’s disease
Symptoms [6]
Signs [8]

Answer 7

Symptoms:

• Easy bruising, Acne
• Mood change
• irregular periods
• Recurrent Achilles tendon rupture
• Increased hair growth
• Swelling, weight gain

Signs:

• DM
• HTN, HF due to Na retention
• Thin purpuric skin, pink striae
• Proximal myopathy, atrophy
• Osteopororsis
• Facial mooning & plethora, pendulous breasts, abdomen
• Edema, central obesity, supraclavicular fat, buffalo neck hump
• Virilisation (masculinization)

Question 8

What are the various causes of Cushing’s? [6]

Answer 8

ACTH dependant:

• Pituitary Tumour ‘Cushings disease’
• Ectopic ACTH (SCLC)

ACTH independent:

• Adrenal adenoma 5-10% producing cortisol
• Adrenal carcinoma is rare
• CCS therapy
• Carney complex
• Micronodular adrenal dysplasia

Pseudo-Cushing’s: alcohol excess, severe depression

Question 9

Cushing’s disease investigation algorithm

Answer 9

Tests to confirm Cushing’s syndrome:

1. Overnight dexamethasone suppression test
   - 1mg oral at midnight then serum cortisol at 8am
2. 24h urine cortisol

Localisation test
1. Paired morning & midnight ACTH-Cortisol
- If ACTH undetectable > ACTH-independent
- If ACTH detectable > ACTH dependent
2. High dose dexamethasone suppression test
8mg

Question 10

What can cause hyperprolactinaemia?

Split into 3 categories - give at least 2 eg of each

Answer 10

Physiological

• Pregnancy
• Lactation/stress
• Stress

Pharmacological
* Dopamine antagonists or DA depleting
* Oestrogens (doesn’t include OCP)
* Antidepressants

Pathological
* Primary hypothyroidism
* Pituitary tumour

Question 11

Give an example of each drug (DA depleting and DA antagonist) that causes hyperprolactinemia

How do we classify prolactinoma that also influences the treatment that it receives? [2]

Answer 11

Neuroleptics eg chlorpromazine
Anti-emetics eg metoclopramide

A microprolactinoma is <10mm
A macroprolactinoma is >10mm

Question 12

How does hyperprolactinaemia present in women [3] and men [6]

Answer 12

Women:

• Galactorrhoea
• Menstrual irregularity
• Infertility

Men:

• Impotence
• Visual field abnormalities
• Headache
• Extraocular muscle weakness
• Other pituitary malfunction
• Eventual galactorhea

Men present later due to less obvious early warning symptoms

Question 13

Investigation [2]

How do you manage hyperprolactinaemia? [1]

Answer 13

Test Serum PRL
Elevated? –> Pituitary MRI
Treat with dopamine agonist Cabergoline

Question 14

What is the primary management for all pituitary tumours?

Compare to this to the management of prolactinomas and give a reason for this difference [2]

Answer 14

• Transphenoidal surgery to remove it +/- radiotherapy
• Dopamine agonists - bromocriptine, cabergoline (1xweekly) can shrink prolactinomas.
• Surgery is usually not indicated due to high response rate

Question 15

What are the signs of hypopituitarism? [5]

What are 2 signs specific to hypopituitarism in children

Answer 15

Tiredness, Weight gain, Depression
Lost libido, Impotence
Menstrual problems
Skin pallor
Reduced body hair

Children: reduced linear growth, delayed puberty

Question 16

What is Cranial Diabetes Insipidus?

Question 17

How does CDI present? [2]

What are the dangerous sequelae? [2]

Answer 17

No vasopressin means huge amounts of urine [1] and consequent thirst [1]

Risk of dehydration [1] & hypokalemia [1]

Question 18

What causes CDI? [4]

Answer 18

Cranial DI - NO secretion of ADH
Nephrogenic - decreased sensitivity to ADH
Gestational DI - degradation of vasopressin by placental vasopressinase
Primary polydipsia - primary defect in osmoreg of thirst

Question 19

How do we test for CDI? [3]

Answer 19

Water deprivation test [1] - deprive fluids for 8h [1] then introduce desmopressin 2mcg [1]

• Cranial DI: responds to ADH causing increase serum osmolality (kidneys are responsive)
• Nephrogenic DI: unable to respond to ADH, kidneys dont respond. Urine osmolality stays low.

Question 20

What could a pituitary tumour press on? [2]

Answer 20

• Optic chiasm

- Cavernous sinus nerves

Question 21

Causes of pituitary hypofunction [4]

Answer 21

Craniopharyngioma
Trauma
Infection - TB, sarcoidosis
Sheehan’s syndrome

Question 22

Management of cranial DI
Mild cases [1]
Main rx [1]
Monitoring [1]

Emergency management [5]

Answer 22

If mild, drinking water can do the trick [1]
Physiological replacement of desmoproressin [1]
Measure serum sodium 1-3 monthly for high Na

Emergency mx:

• ABCDE
• Urgent U&E, serum and urine osmolality, monitor urine output
• Fluids: hypernatremic 0.9% saline with aim of reducing Na no more than 12 mmol/L per day
• Desmopressin

Question 23

In testing for acromegaly, why is it not wise to rely on random testing of Growth Hormone?

Answer 23

• GH: DO NOT rely on random testing as secretion is pulsatile and levels in acromegaly can overlap with normal pulsations and GH is also elevated in stress, sleep, puberty and pregnancy

Question 24

Mx Cushing's disease:
Iatrogenic
Cushing's disease
Adrenal adenoma
Adrenal carcinoma [3]
Ectopic ACTH
Severe ACTH associated

Answer 24

1. Stop CCS
2. Cushing’s disease: transphenoidal excision of pituitary adenoma
3. Adrenal adenoma: adrenalectomy
4. Adrenal carcinoma: adrenalectomy, RT, adrenolytic drugs (mitotane)
5. Ectopic ACTH: surgery
6. Severe ACTH associated psychosis - intubation, mifepristone, etomidate

Question 25

Cushing's disease vs syndrome [2]

Answer 25

Cushing's Disease - pituitary source of ACTH | Cushing's Syndrome - ACTH independent ie adrenal tumor or exogenous CCS

Question 26

What is the effect of pegvisomant on Acromegaly

Answer 26

very effective - decreases IGF-1 levels in 90% of patients to normal doesn't reduce tumour volume therefore surgery still needed if mass effect

Question 27

Hypopituitarism causes [5]

Answer 27

* congenital empty sella * pressure from pituitary tumours * post-irradiation * post-surgery * pituitary infarction

Question 28

Hypopituitarism Investigations

Answer 28

* Baseline bloods - 09.00 hours cortisol, LH/FSH, oestradiol, testosterone, TSH and fT4, prolactin * Insulin tolerance test ITT or glucagon test to confirm GH and ACTH reserve * Hypoglycaemia and glucagon should cause increase in cortisol and GH where pituitary is functioning * GnRH stimulation is rarely used to assess gonadotrophins.

Question 29

Management of hypopituitarism

Answer 29

* Hormone replacement therapy is essential. * ACTH deficiency is treated with hydrocortisone replacement in a regime similar to that in adrenal insufficiency (e.g. 10 mg on waking, 5 mg at midday and 5 mg at 18.00 hours) * Similarly, the resulting secondary hypothyroidism is treated with levothyroxine and gonadotrophins with oestrogen or testosterone. * It is important to replace or confirm ACTH reserve before commencing thyroxine as the resulting increase in metabolism could otherwise precipitate an Addisonian crisis. 690 * In adults, replacement of GH (subcutaneously) will often relieve symptoms of low mood and fatigue.

Question 30

# Water deprivation test & post- DDAVP test What is the diagnosis if Urine osmolality after water deprivation remains <300 Post desmopressin test, the urine osmolality is >600

Answer 30

Cranial DI

Question 31

# Water deprivation test & post- DDAVP test What is the diagnosis if urine osmolality after water deprivation is <300 Post desmopressin is <300

Answer 31

Nephrogenic DI

Question 32

# Water deprivation test & post- DDAVP test What is the urine osmolality result for psychogenic polydipsia for post-water deprivation and post-desmopressin

Answer 32

Both remain >400