Hypersecretion Of Anterior Pituitary Hormones Flashcards
Hyperpituitarism
Symptoms associated with excess production of adenohypophysial hormones
Usually due to isolated pituitary tumours but can also be ectopic (i.e. from non-endocrine tissue) in origin
Can quite often be associated with visual field and other (e.g. cranial nerve) defects
As well as endocrine-related signs and symptoms
Bitemporal hemianopia
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Excess ACTH (corticotrophin) can result in…?
Cushing’s disease
Excess TSH (thyrotrophin) can result in…?
Thyrotoxicosis
Excess gonadotrophins (LH and FSH) can result in…?
Precocious puberty in children
Excess prolactin can result in…?
Hyperprolactinaemia
Excess GH can result in…?
Gigantism, acromegaly
Hyperprolactinaemia
Physiological
- pregnancy
- breastfeeding
Pathological
- prolactinoma (often microadenomas < 10mm diameter)
- prolactinoma = most common functioning pituitary tumour
- high prolactin suppresses GnRH pulsatility
Hyperprolactinaemia due to pituitary adenoma
In women:
- galactorrhoea (milk production) - secondary amenorrhoea (or oligomenorrhoea) - loss of libido - infertility
In men:
- galactorrhoea uncommon (since appropriate steroid background usually inadequate) - loss of libido - erectile dysfunction - infertility
Regulation of prolactin secretion
Inhibitory regulation by dopamine
Lactotrophs —> prolactin
Lactotrophs express D2 receptors
Dopamine from hypothalamic dopaminergic neurones = no prolactin released
Pharmacologically D2 recpetor agonists can be used
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Treatment of hyperprolactinaemia
Medical treatment is 1st line
- dopamine receptor (D2) agonists
Decrease prolactin secretion
Reduce tumour size
Examples:
- Bromocriptine
- Cabergoline
Oral administrationSide effects of dopamine receptor agonists
Nausea and vomiting Postural hypertension Dyskinesias Depression Impulse control disorder (e.g. pathological gambling, hypersexuality)
Excess growth hormone
In childhood = gigantism
In adulthood = acromegaly
Usually due to benign growth hormone secreting pituitary adenoma
Acromegaly
Insidious in onset
Signs and symptoms progress gradually (can remain undiagnosed for many years)
Untreated, excess GH is associated with increased morbidity and mortality
Death:
- cardiovascular disease 60%
- respiratory complications 25%
- cancer 15%
What grows in acromegaly?
Periosteal bone Cartilage Fibrous tissue connective tissue Internal organs (cardiomegaly, splenomegaly, hepatomegaly, etc.)
Clinical features of acromegaly
Excessive sweating (hyperhidrosis)
Headache
Enlargement of supraorbital ridges, nose, hands and feet, thickening of lips and general coarseness of features
Enlarged tongue (macroglossia)
Mandible grows causing protrusion of lower jaw (prognathism)
Carpal tunnel syndrome (median nerve compression)
Barrel chest, kyphosis
Metabolic effects of acromegaly
- Excess growth hormone
- Increased endogenous glucose production, decreased muscle glucose uptake
- Increased insulin production = increased insulin resistance
- Impaired glucose tolerance
- Diabetes mellitus
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Complications of acromegaly
Obstructive sleep apnoea
- bone and soft-tissue changes surrounding the upper airway lead to narrowing and subsequent collapse during sleep
Hypertension
- direct effects of Gh and/or IGF-1 on vascular tree
- GH mediated renal sodium reabsorption
Cardiomyopathy
- hypertension, DM, direct toxic effects of excess GH on myocardium
Increased risk of cancer
- colonic polyps, regular screening with colonoscopy
Co-secretion of prolactin and grwoth hormone in acromegaly
Prolactin is often high in acromegaly - may reflect tumour secreting GH and prolactin
Hyperprolactinaemia will cause secondary hypogonadism
Regulation of GH secretion
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Diagnosis of acromegaly
GH pulsatile - so random measurement unhelpful Elevated serum IGF-1 Failed suppression (‘paradoxical rise’) of GH following oral glucose load - oral glucose tolerance test
Glucose-induced suppression of growht hormone secretion in acromegaly
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Treatment of acromegaly
Surgery (trans-sphenoidal) - 1st line
Medical
- somatostatin analogues (e.g. octreotide)
- dopamine aggonists (GH secreting pituitary tumours frequently express D2 receptors) (e.g. cabegoline
Radiotherapy
Somatostatin analogues
‘Endocrine cyanide’
Injection: sc (short acting) or monthly depot
Gi side effects common (e.g. nausea, diarrhoea, gallstones can occur)
Reduces Gh secretion and tumour size
Pre-treatment before surgery may make resection easier
Use post-operatively if not cured or whilst waiting for radiotherapy to take effect (slow)
