L2 HPA axis Flashcards
Briefly explain the HPA axis
Stress (both psychological and physical) leads to CRH release from hypothalamus, which stimulates ACTH release from pituitary and subsequent cortisol release from adrenal cortex. This is known as the hypothalamic-pituitary-adrenal axis.
What are neuroendocrine mediators?
Substances that function as neurotransmitters, neural hormones and classic hormones e.g. oxytocin, ADH, dopamine, somatostatin
Role of ADH/vasopressin
- osmoregulation
- regulation of ECF volume
Role of oxytocin
regulation of uterine contractions and milk ejection
What is the anterior and posterior hypothalamus involved in?
thermoregulation
Posterior pituitary hormones
- arginine vasopressin (AVP)/ADH
- oxytocin
Which hormone is most commonly secreted in excess amounts by pituitary adenomas?
Prolactin (PRL)
Pituitary and hypothalamic disorders
- Pituitary hypersecretion
- Pituitary insufficiency
- Hypopituitarism
Which patients usually have elevated PRL?
those with hypothalamic disorders and pituitary stalk compression
PRL measurement should be performed in patients presenting with…
- galactorrhoea
- gonadal dysfunction
- secondary gonadotropin deficiency
- enlargement of the sella turcica
Hypersecretion of GH can lead to?
acromegaly
Hypersecretion of ACTH can lead to?
Cushing disease
What is panhypopituitarism?
the lack of all pituitary hormones
- present in <20% of patients with pituitary adenomas
What is the earliest clinical manifestation of a pituitary adenoma in adults?
Hypogonadism, secondary to elevated levels of PRL, GH, or ACTH and cortisol
Hypogonadism in patients with a pituitary adenoma is due to…
interference with GnRH secretion, rather than destruction of anterior pituitary tissue
What is done first to exclude primary gonadal failure in patients with hypogonadism?
screened with FSH and LH measurements
What is the most frequent clinical presentation of hypothalamic-pituitary dysfunction in children?
short stature
- GH deficiency should be considered in these children
TSH or ACTH deficiency is relatively unusual and if present, usually indicates __.
panhypopituitarism
What are commonly associated with secondary hypothyroidism or hypoadrenalism?
panhypopituitarism and large pituitary tumours
What are the most common pituitary tumours in adults?
Prolactinomas
What is hypopituitarism manifested by?
diminished or absent secretion of one or more pituitary hormones
Hypopituitarism is either
- a primary event caused by destruction of the anterior pituitary gland, or
- a secondary phenomenon resulting from deficiency of hypothalamic stimulatory factors normally acting on the pituitary
In general, acquired loss of anterior pituitary function follows what sequence?
GH, LH/FSH, TSH, ACTH, PRL
What does hypopituitarism treatment and prognosis depend on?
- the extent of hypofunction
- the underlying cause
- the location of the lesion in the hypothalamic-pituitary axis
9 I’s for hypopituitarism causes
invasive, infarction, infiltrative, injury, immunologic, iatrogenic, infectious, idiopathic, isolated
What are characteristically seen in the hypersecretory states (excess PRL, GH, ACTH), and can lead to hypopituitarism?
small pituitary tumours called microadenomas
Hypopituitarism may be the initial clinical manifestation of which infiltrative disease processes?
sarcoidosis, haemochromatosis, Langerhans histiocytosis
Severe head trauma may cause…
anterior pituitary insufficiency and diabetes insipidus
What autoimmune condition of the pituitary gland can result in anterior hypopituitarism? Who is most commonly affected?
Lymphocytic hypophysitis
- occurs mostly in women during pregnancy or in the postpartum period
- may present as a mass lesion of the sella turcica with visual field disturbances simulating pituitary adenoma
Effect of radiation therapy to treat pituitary tumours
50-60% incidence hypothalamic and pituitary insufficiency - these patients often have modest hyperprolactinemia, with GH and gonadotropin failure. TSH and ACTH deficiencies less common.
GH deficiency has been associated with mutations in which genes?
those necessary for normal pituitary development
Treatment of ACTH deficiency/secondary adrenal insufficiency
must include glucocorticoid support i.e. hydrocortisone or prednisone, like primary adrenal failure
- the minimum effective dosage should be given to avoid iatrogenic hypercortisolism
Treatment of TSH deficiency/secondary hypothyroidism
must be based on clinical grounds and the circulating concentration of serum thyroxine
Aim of treatment of secondary hypogonadism
to replace sex steroids and restore fertility
Treatment of gonadotropin deficiency/secondary hypogonadism
- oestrogen and progesterone
- ovulation induction (in women with hypothalamic-pituitary dysfunction)
- androgens (for both women and men)
- spermatogenesis (combined use of hCG and recombinant FSH)
What medication can be used in patients with gonadal failure of hypothalamic origin (i.e. infertility) to induce ovulation?
Clomiphene Citrate
What is used for children with hypopituitarism and adults with GH deficiency and known pituitary disease?
human growth hormone (hGH) produced by recombinant DNA technology
- adults: administered subcutaneously once daily (dosage: 2-5 µg/kg)
Contraindications to GH therapy
- presence of diabetic retinopathy
- active malignancy
- intracranial hypertension
- radiotherapy
- airway obstruction in individuals with Prader-Willi Syndrome
What drug is a synthetic version of somatostatin that is used to treat gigantism and acromegaly?
Octreotide
Adverse effects of Octreotide
GI disturbances, gallstones, hyperglycaemia, acute hepatitis
Synthetic analogue of thyrotrophin-releasing hormone (TRH)
Protirelin - used in the diagnosis of thyroid disease
What is Somatropin and what is it used for?
hGH analogue, used to treat pituitary dwarfism and childhood renal insufficiency
Adverse effects of Somatropin
gigantism in children and acromegaly in adults
What drug inhibits prolactin effects and is used to treat prolactinomas?
Bromocriptine
ADH analogues used to treat diabetes insipidus and vasoconstriction
desmopressin, terlipressin
Which drugs increase ADH effects?
NSAIDs and carbamazepine
Which drugs decrease ADH effects?
Lithium, colchicine (used to treat gout), vinca alkaloids (diabetes & hypertension treatment, disinfectants, anti-cancer)
Which drug counteracts ADH?
Demeclocycline
What causes Addison’s disease?
Caused by APECED (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)
Adrenal glands do not produce sufficient steroid hormones, which leads to chronic adrenal insufficiency.
How is acute adrenal insufficiency managed?
- Dextrose/NaCl IV
- Hydrocortisone (cortisol)
Causes of acute adrenal insufficiency
- lesions secondary to surgery
- abrupt withdrawal of glucocorticoids (high dose/prolonged use)
Symptoms of acute adrenal insufficiency
GIT symptoms, low Na+, high K+, weakness, lethargy, hypotension
Common symptoms of Addison’s disease
hyperpigmentation, weight loss, weakness, fatigue, hypotension, inability to maintain fasting blood sugar
Management of Addison’s disease
- Hydrocortisone
- Fludrocortisone acetate
Indicator of adequate replacement therapy in chronic adrenal insufficiency
- disappearance of hyperpigmentation and electrolyte imbalances
- plasma ACTH levels monitored and urinary free cortisol, adjust dosage for stress
Causes of Cushing’s syndrome
- pituitary adenoma
- tumour of the adrenal gland
Symptoms of Cushing’s syndrome
round plethoric face, truncal obesity, muscle wasting, thinning purple striae, poor wound healing, osteoporosis
Management of Cushing’s syndrome
- Surgery
- Hydrocortisone
