16. Pituitary And Adrenal Disorders

Question 1

How do you asses the pituitary gland?

4

Answer 1

1. Insulin tolerance test: IV insulin 0.15 u/kg
   a. Requires adequate hypoglycaemia (glucose < 2.2 mml/l)
   b. Tests GH and ACTH/Cortisol production
   —> Normal GH: > 5 ng/ml
   —> Normal cortisol: > 500 nM
   —> C/I: seizures, IHD
2. Short Synacthen test (SST):
   a. I.M Synacthen (synthetic ACTH)
   b. Check cortisol at Baseline and at 30 mins
   c. Indirect test of pituitary-adrenal axis
   d. Normal response cortisol: > 500 nM at 30mins
3. Thyroid axis: check free T4, TSH
   a. Secondary hypothyroidism: low FT4, low or normal (inappropriately low) TSH
4. Gonadal axis: check testosterone, Estradiol, LH/ FSH
   a. Deficiency:
   —> Men: low testosterone with low or normal LH/FSH
   —> Women: amenorrhea  low oestradiol with low or normal LH/FSH // in post menopausal women, inappropriately low FSH/LH

Question 2

How is the pituitary gland interpreted?
(3)

What is the managment of pituitary macroadenomas?
(3)

Answer 2

INTERPRETATION
1. Poor cortisol and GH response to hypoglycaemia: ACTH and GH deficiency (low IGF-1 supports diagnosis of GH deficiency)

2. Low testosterone with “ inappropriately low LH and FSH: central hypogonadism/hypogonadotrophic hypogonadism
3. Low T4 with “ inappropriately” low TSH: central hypothyroidism

Management
1. Hormone replacement
a. Hydrocortisone followed by:
—> Thyroxine
—> Testosterone

2. Surgical decompression: transcranial vs trasnphenoidal
3. Post-op radiotherapy: 50.4 Gy

Question 3

What is acromegaly?

What effects does it cause? See ppt slide 23.
(3)

What is the treatment?
(5)

Answer 3

• Abnormal growth of hands, feet, and face b/c of overproduction of GH by pituitary gland

EFFECTS

1. Tumour expansion: headaches, visual defects, cranial nerve palsies
2. GH hypersecretion: morphological, endocrine, and metabolic change —> can lead to: a real swelling, bony changes to facial features, organomegaly, skin tags, colonic polyps, insulin resistance, DM or IGT, hypertension, LV hypertrophic, cardiac death
3. Hypopituitarism: lethargy, weakness, infertility, loss of libido

TX 
1.	Surgery
2.	Radiotherapy
3.	Medical therapy
a.	Pituitary targeted: reduce GH secretion
—> Dopamine agonists: Cabergoline
—> Somatostatin analogues: Octreotide, Lanreotide
b.	GH receptor blocker: Pegvisomant
4.	Replacement of pituitary hormones
5.	Treat co-morbidities (hypertension

Question 4

What is adrenal gland insufficiency (primary vs secondary)?

What are the causes?
(8)

What is the clinical presentation?
(2)

What is the pathology?
(4)

Answer 4

Primary: disorder to adrenal glands —> Addison’s Disease
Secondary: inadequate secretion of ACTH by pituitary gland

CAUSES

1. Autoimmune
2. TB
3. Bilat Adrenalectomy
4. Granulomas
5. Haemochromatosis
6. Sarcoidosis
7. Waterhouse Friederichsen
8. Metastases

CP

1. Weight loss
2. Pigmentation

PATHO:

1. Loss of adrenal cortex with low circulating
2. Cortisol: fatigue, weight loss, poor healing, hypoglycaemia, hypotension
3. Aldosterone: hypotension, hyponatraemia hyperkalaemia, dehydration
4. Androgens: loss of libido (women), low quality of life, high ACTH (pigmentation), renin

Question 5

What is primary aldosteronism (Conn’s Syndrome)?

What is the clinical presentation?
(2)

What are the causes?
(4)

Answer 5

Aldosterone excess

• Inappropriate sodium retention mediated via mineralcorticoid receptor
• Suppression of plasma renin activity

CP

1. Hypertension
2. Hypokaleamic alkalosis

CAUSES

1. 1. Aldosterone producing adenoma: autonomous secretion
2. Bilateral idiopathic adrenal hyperplasia: exaggerated aldo response to Ang II
3. Primary hyperplasia, carcinoma
4. Glucocorticoid-suppressive hyperaldosteronism

Question 6

What is Cushing’s Syndrome?

What are the 3 types?

What is the clinical presentation?
(9)

How do you diagnose it?
(3)

What is the management?
(3)

Answer 6

Gluticorticoid excess
Metabolic disorder caused by overproduction of cortoicerstoid hormones by adrenal cortex

1. 1. Iatrogenic
2. ACTH dependent (pituitary Cushing’s)
   - ACTH producing pituitary adenoma: Cushing’s disease
   - Ectopic ACTH production
3. ACTH independent (adrenal Cushing’s)
   - Cortisol-producing adrenal tumours
   - Adrenocortical hyperplasia

ACTH Dependent vs Independent

1. Measure ACTH
2. Suppressed levels = adrenal source
3. Normal or raised levels = pituitary Cushing’s or ectopic ATCH production

CP

1. CVS: dysplipidemia, hypertension, thrombosis, vascultiis
2. CNS: changes in behaviour, cognition, memory, mood (glucocorticoid-induced psychoses), cerebral atrophy
3. GI: bleeding, pancreatitis, peptic ulcer
4. Immune system: broad immunosuppression, activation of latent viruses
5. Integument: atrophy, delayed wound healing, erythema, hyper triceps is, telangiectasia, straie rubrae, petechiae, perioral dermatitis
6. MSK: bone necrosis, muscle atrophy, osteoporosis
7. Eyes: cataracts, glaucoma
8. Kidney: increased sodium retention and potassium secretion
9. Reproductive: delayed puberty, fetal growth retardation, hypogonadism

DX

1. Outrule or treat alcoholism and depression (if present)
2. Assess overall cortisol secretion: 24 urine free cortisol
3. Assess cortisol rhythm/dynamics
   - 1 mg overnight dexamethasone suppression test
   - Low dose 48 hr dexamethasone suppression test
   - Late -night salivary cortisol

MANAGEMENT

1. Surgical:
   - Transsphenoidal surgery for pituitary adenoma
   - Adrenalectomy (adrenal Cushing’s or failed pituitary surgery)
2. Pituitary radiotherapy
3. Medical treatment: metyrapone, ketoconazole, aminoglutethimide, RU 486