Acromegaly and prolactinoma Flashcards
Pathogenesis of acromegaly & gigantism?
- Hormonal disorder in adults where there is excess secretion of GH from pituitary
- This leads to continued growth of the extremities
- In children, excess GH causes gigantism as long bones’ epiphyseal plates haven’t fused yet
When does the hypothalamus release GHRH?
Effect on pituitary and mechanism of negative feedback?
- Pulsatile manner
- Low BG levels
- Lack of food
- Increased exercise
- Increased sleep
- Increased stress or trauma
Neg feedback:
- GHRH goes to the anterior pituitary
- GHRH binds to surface protein on somatotroph cells of the anterior pituitary and this causes release of growth hormone
- GH is controlled by negative feedback from liver, bones, muscle (produce somatomedins which signal the anterior pit to stop producing GH)
- Too much GHRH signals hypothalamus to stop producing GHRH
- GH + somatomedins = hypothalamus produces somatostatin (GHIH) to signal the anterior pituitary to stop producing GH
Effects of growth hormone in the body
Direct effects:
- liver = more glucose into blood
- muscle = body retains nitrogen leading to muscle growth
- bones = osteoblasts get stimulated to increase bone thickness
- increase insulin resistance (diabetogenic effect)
Indirect effects:
- stimulates the liver, skeletal muscle, bone and kidney to produce IGF-1
- IGF-1 promotes cellular metabolism, prevents cell death, helps cells divide and differentiate
What is the main cause of acromegaly?
Pituitary adenoma (tumour of somatotroph cells in anterior pituitary which continue to make GH leading to excess IGF-1)
Symptoms & clinical features of acromegaly
- Acral enlargement (hands, feet, jaw)
- Arthralgias (joint pain)
- Maxillofacial changes. (bottom incisors infront of top)
- Excessive sweating
- Headache
- Hypogonadal symptoms (erectile dysfunction, depressed mood, decreased libido, sleep disturbances)
What are some common co-morbidities associated with acromegaly? What impact does this have on survival?
- Hypertension
- Congestive heart failure
- Cerebrovascular and headaches
- Arthritis
- Insulin resistant diabetes
- Sleep apnoea
- Carpal tunnel syndrome
- 10 year life reduction expectancy
What 3 things do we do to diagnose acromegaly?
Clinical features
Hormone levels
IGF-1
What result do we see in patients with acromegaly and those without after a 75mg oral glucose tolerance test?
GH is not suppressed in these patients after having glucose
Normal response = suppressed to 1ug/mL (0.2ug/mL being used more now)
What is the primary therapy for acromegaly?
Benefits and Drawbacks
Pituitary surgery
Benefits
- cost effective
- rapid fall in GH
- prospect of a cure
Drawbacks
- depends on experience of surgeon
- depends on size of tumour (if >1cm cure rate 50%, <1cm cure rate is good)
- complications of surgery (more common in inexperienced surgeons)
What medical therapy is available for acromegaly?
1. Dopamine agonists Switch off GH production - cabergoline or - bromocriptin (less effective than cabergoline & more side effects) - Oral administration
- Somatostatin analogues (USED NOW)
- Octreotide and lancreotide commonly used now as they last longer in the blood
- Work by turning off GH
- More effective than cabergoline
- Monthly injections
- Upset stomach main side effect - Growth hormone receptor antagonists
- Pegvisomant new
- prevents action of GH so you don’t produce IGF-1
- Subcut injection (half life 70hrs)
- Expensive so tightly regulated by NHS
- Effective medication
What other treatments excluding medical and surgical are there for acromegaly & What types are there?
Radiotherapy on pituitary
- Conventional radiotherapy (smaller dose but includes optic nerve and causes deficiency in other hormones)
- Sterotactic
(single fraction causes less radiation to surrounding tissue - doesn’t affect optic nerve)
- Gamma knife
- LINAC
- Proton beam
(precise deposition on pituitary - hard to access, only 2 in England)
What do lactotroph cells secrete? Where are they found?
Found in the anterior pituitary, secrete Prolactin
How is prolactin release controlled?
- Prolactin release is controlled by the hypothalamus
- The hypothalamus makes 2 key hormones:
- Thyrotrophin releasing hormone which increases prolactin release
- Dopamine which inhibits prolactin release and overrides the stimulatory effect of thyrotrophin releasing hormone
- Dopamine is the prolactin-inhibiting factor - which is constantly released to prevent prolactin release in anyone who is not pregnant
- High levels of prolactin in the blood sends a negative feedback signal to the hypothalamus making it release more dopamine which decreases prolactin
What is a prolactinoma?
What effects can it have on structures?
Functional tumour which secretes high levels of prolactin
<10mm in diameter = microprolactinoma
> 10mm in diameter = macroprolactinoma
They can compress surrounding structures such as the optic nerve as they cross the optic chiasm = visual problems such as bitemporal hemianopia (tunnel vision)
How can high prolactin cause infertility and increased risk of fractures?
- Prolactin inhibits hypothalamus from releasing gonadotrophin releasing hormone which leads to less FSH and LH from pituitary
- This results in less oestrogen being produced in ovaries and less testosterone from the testes
- Low levels of sex hormones can inhibit ovulation in women and spermatogenesis in men
- Oestrogen is important in women as it also prevents the activation and differentiation of osteoclasts which break down bone and release calcium into blood
- With decreased oestrogen, osteoclasts are free to proliferate and therefore, women with prolactinomas are at increased risk of fractures and osteoporosis
