Cushings and Hypopituitarism Flashcards
Screening Tests for Cushings
Definitive Tests for Cushings
Screening: -1mg dexamethasone suppression test -Urine free cortisol test (<250 is normal) -Diurnal cortisol variation Definitive: 2 day 2mg/day dexamethasone
Aetiology of Cushings
Pituitary (80% plus) Adenoma of adrenal Benign cancer Ectopic Thymus Lung Pancreas Pseudo Alcohol and Depression Steroid medication
When treatng cushings, what would you do if hypophysectomy did not work?
External radiotherapy
How would you treat ectopic cushings?
Bilateral adrenalectomy if you cannot find source etc
Drug treatment for cushings if other treatment does not work
Metyrapone- if other treatments fail - while waiting for radiotherapy to work- S/E common
Ketoconazole
Pasireotide- new somatostatin analogue
Autoimmune causes of hypopituitarism
Sheehans
Secondary metastatic lesions that could cause hypopituitarism
Breast, lung
Local brain tumours
Astrocytoma
Meningioma
Glioma
Granulomatous diseases that could cause hypopituitarism
TB
Sarcoidosis
Histiocytosis X
Vascular disease that could cause hypopituitarism
Polyarteritis
Hypothalamic diseases that could cause hypopituitarism
Syphilis
Meningites
Causes of hypopituitarism
Pituitary Tumours Secondary metastatic lesions lung, breast Local brain tumours Astrocytoma, meningioma, glioma Granulomatous diseases TB, Histiocytosis X, sarcoidosis Vascular diseases Polyarteritis Trauma road accidents, skull fractures Hypothalamic diseases Syphilis, meningitis Iatrogenic; surgery Autoimmune;Sheehan – post pregnancy Infection; meningitis
Signs and symptoms of anterior hypopituitarism
Menstrual irregularities (F) Infertility, impotence Gynaecomastia (M) (testosterone deficiency) Abdominal obesity Loss of facial hair (M) Loss of axillary and pubic hair (M&F) Dry skin and hair Hypothyroid faces growth retardation (children)
Testing for Hypopituitarism
Baseline pituitary function tests
fT4, TSH
Oestradiol/Testosterone, LH FSH
GH, IGF-1
Prolactin
Replacement therapy for hypopituitarism
Thyroxine 100-150mcg/day Hydrocortisone 10-25 mg/day (am/pm) ADH Desmospray (nasal) or tablets GH GH nightly sc Sex Steroids Oest/prog pill for F, Testosterone for males
Growth hormone and bone density?
GH increases bone density
Growth hormone and muscle mass?
GH increases muscle mass, strength, exercise capacity and stamina
GH and abdominal obesity
GH decreases abdominal obesity
GH and cardiac function
GH improves cardiac function
GH and cholesterol and LDL
Decreases cholesterol and LDL
How is GH administered?
Daily by subcutaneous injection
Testosterone replacement
IM injection every 3-4 weeks (sustanon) Skin gel (testogel, tostram) Prolonged IM injection 10-14 wks (nebido) (Oral tablets (restandol))
Intramuscular injection that can be given as testosterone replacement?
Sustanon
-Given every 3-4 weeks
Restandol is an oral testosterone replacement. What are the risks of tablet oral testosterone?
Hepatitis
Risks of Testosterone Replacement
Prostate Enlargement. Does NOT cause prostate cancer but may make it grow - monitor PR exam and PSA
Polycythaemia - monitor FBC
Hepatitis (only for oral tablets) - monitor LFTs
Causes of Cranial Diabetes Insipidus
Familial isolated in most cases DIDMOAD (DI, DM, optic atrophy, deaf) Acquired Idiopathic in 50% Trauma; road accidents, surgery, skull fracture RARE Tumour, sarcoid, ext irradiation, meningitis
Most common type of pituitary gland tumour
Prolactinoma
Symptoms of a prolactinoma
Headaches or reduced vision if prolactinoma is pressing on brain or nerves nearby
Irregular periods or no periods.
Reduced fertility.
Reduced sex drive.
Milk leaking from the breasts (known as galactorrhoea). The milk may leak out by itself, or may only show when the breast is squeezed. (Note: leakage of milk from the breasts is normal towards the end of pregnancy, with recent childbirth, if breast-feeding, and for some time after finishing breast-feeding.)
Increased growth of hair on the face or body.
MEN may have:
Reduced fertility.
Erectile dysfunction (difficulty having an erection).
Reduced sex drive (libido).
Breast enlargement (called gynaecomastia).
Very rarely, leakage of milk from the breasts.
Normal levels of prolactin
5000mU/L
Drugs that can increase prolactin levels
Risperidone, clopramide, domperidone
Somatostatin and GH
Somatostatin analogues are currently used as treatment for GH acromegaly, they may also be used to shrink large tumours before surgery. They are synthetic analogues of somatostatin which inhibits GH production
-Injected every 2-4 weeks for effective treatment
What type of receptor does TSH bind to?
Surface receptors
This then activates G proteins and conversion of GTP to GDP and production of cAMP
cAMP increases production and release of T3 and T4
T3 and T4 circulate in bound and free forms
On release T3 and T4 bind to receptor in target cells.
Complex translocates to the nucleus
Binds to Thyroid Response Elements on target genes
Stimulates transcription of these genes
Increase BMR
Struma ovarri
“goitre of the ovary”
Contains thyroid tissue
Can you get a TSH secreting adenoma?
Yes, but rare
Causes of hyperthyroidism
Symptoms and signs occur as a result of excess T3 and T4
85% are due to Grave’s disease
Other causes include hyperfunctioning nodules/tumours and thyroiditis
TSH secreting pituitary adenoma (rare)
Ectopic production (struma ovarii)
Factitious (exogenous intake)
DeQuervains Thyroiditis
De Quervains Thyroiditis: hyperthyroid then hypothyroid, euthyroid. Patients may suffer dysphagia. There are multi-nucleated giant cells on histology
Difference between thyroiditis and Graves disease in radionucleotide isotope uptake?
Thyroiditis = decreased uptake
Graves disease = increased uptake
