Lecture 6.2 - Pituitary disorders.pdf

Pituitary gland: ◦Sits below the brain in the sella turcica (a pocket of the sphenoid bone) Pituitary disorders: ◦Pituitary disorders are relatively rare (~70,000 patients in the UK) ◦Manifest as either OVER or UNDER secretion of pituitary hormones ◦The most common cause is...

Pituitary gland: ◦Sits below the brain in the sella turcica (a pocket of the sphenoid bone) Pituitary disorders: ◦Pituitary disorders are relatively rare (~70,000 patients in the UK) ◦Manifest as either OVER or UNDER secretion of pituitary hormones ◦The most common cause is a benign tumour (adenoma) Clinical presentation of pituitary tumours: ◦Most pituitary tumours are "non-functioning" (the tumour cells do not produce any hormone) ◦Mass effect of tumour on local structures: ‣ Visual loss ‣ Headache ◦Abnormal pituitary function: ‣ Hypo-secretion of pituitary hormones ‣ Hyper-secretion of pituitary hormones ◦Mass effect of pituitary tumour on local structures: ‣ Optic chiasm (vision loss) ‣ III, IV (eye movement) ‣ Va,b (pain) ‣ Internal carotid artery (blood supply) ‣ VI nerve (lateral eye movement) ◦Visual field loss due to pressure on optic chiasm - assessment of visual fields ◦Bi-temporal hemi-anopia - highly suggestive of pituitary tumour Investigation of a suspected pituitary tumour involves: ◦Imaging - size and topographical location of the pituitary or parapituitary mass (usually by magnetic resonance imaging (MRI) scan) ◦Assessment of visual field defects ◦Assessment of endocrine function to determine whether there is a hormonal excess or deficiency - measuring the levels of relevant hormones in  the blood (where possible staining sections from a biopsy of the tumour with antibodies for the relevant hormone) ‣ Abnormal pituitary function - hypo or hyper-secretion of hormones ◦Investigation of a suspected pituitary tumour involves: ‣ Imaging of the area: anatomy, size and topographical location of the pituitary or parapituitary mass ‣ Usually by MRI scan ◦Normal pituitary gland - sagittal and coronal planes: Assessment of endocrine function Hypopituitarism: ◦Hypopituitarism - insufficient production of pituitary hormones ◦Most commonly a result of a pituitary adenoma (rarer causes include radiation therapy, inflammatory disease and head injury) ◦Loss of pituitary hormone secretion is usually secondary to a mass effect of the adenoma ◦Typically progressive loss of anterior pituitary function (GH and LH/FSH are usually the first hormones to be affected) ◦Pan-hypopituitarism - deficiency for ALL anterior pituitary hormones ◦Secretion of antidiuretic hormone (ADH) and oxytocin from the posterior pituitary is usually affected significantly only if the tumour affects the hypothalamic function of if an inflammatory process is involved Growth hormone deficiency: ◦GH deficiency in adults: ‣ GH deficiency in adults is usually due to a mass effect from a pituitary adenoma ‣ Reduced quality of life (reduced sense of wellbeing), decreased tolerance to exercise, decreased muscle strength, increased body fat ◦GH deficiency in children: ‣ Typically of unknown cause (idiopathic) ‣ In some cases it is caused by specific gene mutations (e.g. in the growth hormone releasing hormone receptor) and autoimmune inflammation ‣ Incidence: ~1 in 3800 live births ‣ GH deficiency has little effect on foetal growth ‣ Severe prenatal deficiency can result in hypoglycaemia and jaundice ‣ From ~1 year of age until mid-teens results in poor growth and short stature (treatment: human recombinant GH)  Gonadotropin deficiency: ◦Gonadotropin deficiency in adults: ‣ Gonadotropin deficiency (hypogonadism) due to mass effects from a pituitary adenoma can result in: Loss of secondary sexual characteristics Lack of libido, infertility and oligomenorrhea or amenorrhea in women of reproductive age Decreased libido and impotence in men ‣ Children - delayed puberty TSH and ACTH deficiency: ◦TSH and ACTH deficiency - late features of pituitary tumours ◦TSH deficiency - low thyroid hormones (low T4) and non-elevated TSH, symptoms, feeling cold, weight gain, tiredness, slow pulse ◦ACTH deficiency - low cortisol, symptoms, feeling tired, dizzy, low blood pressure (low sodium) (HPA axis integrity is vital so ACTH deficiency can be life threatening) ADH deficiency - diabetes insipidus: ◦Antidiuretic hormone (ADH; vasopressin) is synthesised in the hypothalamus and is transported to the posterior pituitary for release ◦ADH deficiency (diabetes insipidus) may result from a hypothalamic tumour or a pituitary tumour that has extended up into the hypothalamus (diabetes insipidus is unusual in pituitary tumours which usually affect just the anterior pituitary) ◦Other causes of ADH deficiency: cranial radiotherapy, pituitary surgery, autoimmune infiltration, and infections such as meningitis ◦Insufficient release of ADH from the posterior pituitary leads to excess excretion of dilute urine resulting in dehydration and increased sensation of thirst (polydipsia). This represents the cranial form of diabetes insipidus ◦The nephrogenic form of diabetes insipidus is caused by ADH resistance (the kidneys do not respond to ADH in the normal way) ◦Diabetes insipidus should not be confused with diabetes mellitus Prolactinoma: ◦Prolactinoma -> prolactin-secreting pituitary tumour ◦Macro-adenoma - large tumour (> 1cm) ◦Micro-adenoma - small tumour (< 1cm) ◦The larger the prolactinoma -> the higher the prolactin levels ◦Prolactinomas are typically treated with tablets (not by operation), even in cases when the tumour is large and causes visual problems ◦Prolactin is under a tonic inhibitory control by dopamine, so anything blocking the pituitary stalk will lead to prolactin disinhibition ("stalk effect") ‣ If prolactin < 5000 miU/L - might be due to disinhibition rather than active prolactin secretion ‣ If prolactin > 5000 miU/L - likely due to active prolactin secretion (prolactinoma) ‣ This is important as prolactinomas are treated medically, but non-functioning pituitary tumours are treated surgically  ◦Symptoms of hyperprolactinaemia in women: ‣ Galactorrhoea (unexplained milk production - milky discharge from breasts) ‣ Menstrual disturbance (e.g. amenorrhea, menstrual cycle stops) ‣ Fertility problems (hypogonadism, diminished activity of the ovaries) ◦Symptoms of hyperprolactinaemia in men: ‣ Galactorrhoea is rare in men ‣ Gynecomastia (hard breast tissue) ‣ Fertility problems (hypogonadism, diminished activity of the testes) ◦Points to consider in patients with hyperprolactinaemia: ‣ In a patient with high prolactin levels always check the medications - for example: dopamine antagonists can cause high prolactin levels (anti-sickness, anti-psychotic, anti-depressant drugs) ‣ In women of reproductive age with high prolactin levels - make sure that they are not pregnant ◦Treatment of prolactinaemia: ‣ Dopamine agonists are effective at reducing prolactin (stimulate D2 receptors): Bromocriptine Cabergoline Acromegaly: ◦Acromegaly is caused by growth hormone (GH) secreting pituitary tumours which are typically large (> 10 mm in diameter) and lead to gradual changes in features over time ◦Tell-tale sign is large extremities (hands and feet) ◦In children - excess GH secretion before the fusion of epiphyseal plates in the long bones of the body - GIGANTISM ◦Other changes in physical appearance include: ‣ Course facial features: broad/enlarged nose, thickened lips, protruding lower jaw, enlarged tongue, wider spacing between teeth and a prominent supraorbital ridge (the crest of bone situated on the frontal bone of the skull) ‣ Coarse, oily and thickened skin with excessive sweating ‣ Deepening of the voice due to hypertrophy of the soft tissues of the upper airways ‣ Severe snoring due to obstruction of the upper airway ◦Biochemical testing: ‣ In adults: pulsatile GH secretion (~5 pulses/24 hour) ‣ Highest GH peak occurring at the onset of sleep ‣ Between pulses GH levels are too low to be measured ‣ Mean GH concentration varies throughout life - peaks during puberty and declines in old age ‣ Need to do dynamic tests to determine GH secretion (e.g. oral glucose load to suppress GH secretion) ◦Biochemical tests to confirm acromegaly: ‣ Oral glucose tolerance test (OGTT) with measurement of the GH response (failure to suppress GH to levels < 1 ug/L) ‣ Measurement of IGF-1 blood levels (elevated IGF-1 according to age-related reference range) ‣ Growth hormone day curve (GHDC) (elevated mean GH)  ◦Treatment of acromegaly: ‣ Surgery to remove pituitary adenoma ‣ Drug therapy (dopamine receptor agonists, somatostatin analogs, antagonists of the GH receptor): Dopamine receptor agonists: Cabergoline, Bromocriptine (have some efficacy in reducing GH levels, but requires a much higher dose than that used for prolactin-secreting pituitary adenoma) Somatostatin analogs (SSA): Octreotide, Lanreotide, Pasireotide Antagonists of the GH receotir - Pegvisomant ‣ Radiation therapy External beam - multiple short bursts over several weeks Gamma knife - high concentration over a single session ACTH excess: ◦Excess endogenous secretion of ACTH from the anterior pituitary gland is one of the causes of Cushing's syndrome