L2 HPA axis Flashcards

1
Q

Briefly explain the HPA axis

A

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.

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2
Q

What are neuroendocrine mediators?

A

Substances that function as neurotransmitters, neural hormones and classic hormones e.g. oxytocin, ADH, dopamine, somatostatin

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3
Q

Role of ADH/vasopressin

A
  • osmoregulation
  • regulation of ECF volume
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4
Q

Role of oxytocin

A

regulation of uterine contractions and milk ejection

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5
Q

What is the anterior and posterior hypothalamus involved in?

A

thermoregulation

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6
Q

Posterior pituitary hormones

A
  • arginine vasopressin (AVP)/ADH
  • oxytocin
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7
Q

Which hormone is most commonly secreted in excess amounts by pituitary adenomas?

A

Prolactin (PRL)

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8
Q

Pituitary and hypothalamic disorders

A
  1. Pituitary hypersecretion
  2. Pituitary insufficiency
  3. Hypopituitarism
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9
Q

Which patients usually have elevated PRL?

A

those with hypothalamic disorders and pituitary stalk compression

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10
Q

PRL measurement should be performed in patients presenting with…

A
  • galactorrhoea
  • gonadal dysfunction
  • secondary gonadotropin deficiency
  • enlargement of the sella turcica
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11
Q

Hypersecretion of GH can lead to?

A

acromegaly

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12
Q

Hypersecretion of ACTH can lead to?

A

Cushing disease

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13
Q

What is panhypopituitarism?

A

the lack of all pituitary hormones
- present in <20% of patients with pituitary adenomas

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14
Q

What is the earliest clinical manifestation of a pituitary adenoma in adults?

A

Hypogonadism, secondary to elevated levels of PRL, GH, or ACTH and cortisol

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15
Q

Hypogonadism in patients with a pituitary adenoma is due to…

A

interference with GnRH secretion, rather than destruction of anterior pituitary tissue

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16
Q

What is done first to exclude primary gonadal failure in patients with hypogonadism?

A

screened with FSH and LH measurements

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17
Q

What is the most frequent clinical presentation of hypothalamic-pituitary dysfunction in children?

A

short stature
- GH deficiency should be considered in these children

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18
Q

TSH or ACTH deficiency is relatively unusual and if present, usually indicates __.

A

panhypopituitarism

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19
Q

What are commonly associated with secondary hypothyroidism or hypoadrenalism?

A

panhypopituitarism and large pituitary tumours

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20
Q

What are the most common pituitary tumours in adults?

A

Prolactinomas

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21
Q

What is hypopituitarism manifested by?

A

diminished or absent secretion of one or more pituitary hormones

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22
Q

Hypopituitarism is either

A
  1. a primary event caused by destruction of the anterior pituitary gland, or
  2. a secondary phenomenon resulting from deficiency of hypothalamic stimulatory factors normally acting on the pituitary
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23
Q

In general, acquired loss of anterior pituitary function follows what sequence?

A

GH, LH/FSH, TSH, ACTH, PRL

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24
Q

What does hypopituitarism treatment and prognosis depend on?

A
  • the extent of hypofunction
  • the underlying cause
  • the location of the lesion in the hypothalamic-pituitary axis
25
Q

9 I’s for hypopituitarism causes

A

invasive, infarction, infiltrative, injury, immunologic, iatrogenic, infectious, idiopathic, isolated

26
Q

What are characteristically seen in the hypersecretory states (excess PRL, GH, ACTH), and can lead to hypopituitarism?

A

small pituitary tumours called microadenomas

27
Q

Hypopituitarism may be the initial clinical manifestation of which infiltrative disease processes?

A

sarcoidosis, haemochromatosis, Langerhans histiocytosis

28
Q

Severe head trauma may cause…

A

anterior pituitary insufficiency and diabetes insipidus

29
Q

What autoimmune condition of the pituitary gland can result in anterior hypopituitarism? Who is most commonly affected?

A

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

30
Q

Effect of radiation therapy to treat pituitary tumours

A

50-60% incidence hypothalamic and pituitary insufficiency - these patients often have modest hyperprolactinemia, with GH and gonadotropin failure. TSH and ACTH deficiencies less common.

31
Q

GH deficiency has been associated with mutations in which genes?

A

those necessary for normal pituitary development

32
Q

Treatment of ACTH deficiency/secondary adrenal insufficiency

A

must include glucocorticoid support i.e. hydrocortisone or prednisone, like primary adrenal failure
- the minimum effective dosage should be given to avoid iatrogenic hypercortisolism

33
Q

Treatment of TSH deficiency/secondary hypothyroidism

A

must be based on clinical grounds and the circulating concentration of serum thyroxine

34
Q

Aim of treatment of secondary hypogonadism

A

to replace sex steroids and restore fertility

35
Q

Treatment of gonadotropin deficiency/secondary hypogonadism

A
  1. oestrogen and progesterone
  2. ovulation induction (in women with hypothalamic-pituitary dysfunction)
  3. androgens (for both women and men)
  4. spermatogenesis (combined use of hCG and recombinant FSH)
36
Q

What medication can be used in patients with gonadal failure of hypothalamic origin (i.e. infertility) to induce ovulation?

A

Clomiphene Citrate

37
Q

What is used for children with hypopituitarism and adults with GH deficiency and known pituitary disease?

A

human growth hormone (hGH) produced by recombinant DNA technology
- adults: administered subcutaneously once daily (dosage: 2-5 µg/kg)

38
Q

Contraindications to GH therapy

A
  • presence of diabetic retinopathy
  • active malignancy
  • intracranial hypertension
  • radiotherapy
  • airway obstruction in individuals with Prader-Willi Syndrome
39
Q

What drug is a synthetic version of somatostatin that is used to treat gigantism and acromegaly?

A

Octreotide

40
Q

Adverse effects of Octreotide

A

GI disturbances, gallstones, hyperglycaemia, acute hepatitis

41
Q

Synthetic analogue of thyrotrophin-releasing hormone (TRH)

A

Protirelin - used in the diagnosis of thyroid disease

42
Q

What is Somatropin and what is it used for?

A

hGH analogue, used to treat pituitary dwarfism and childhood renal insufficiency

43
Q

Adverse effects of Somatropin

A

gigantism in children and acromegaly in adults

44
Q

What drug inhibits prolactin effects and is used to treat prolactinomas?

A

Bromocriptine

45
Q

ADH analogues used to treat diabetes insipidus and vasoconstriction

A

desmopressin, terlipressin

46
Q

Which drugs increase ADH effects?

A

NSAIDs and carbamazepine

47
Q

Which drugs decrease ADH effects?

A

Lithium, colchicine (used to treat gout), vinca alkaloids (diabetes & hypertension treatment, disinfectants, anti-cancer)

48
Q

Which drug counteracts ADH?

A

Demeclocycline

49
Q

What causes Addison’s disease?

A

Caused by APECED (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)
Adrenal glands do not produce sufficient steroid hormones, which leads to chronic adrenal insufficiency.

50
Q

How is acute adrenal insufficiency managed?

A
  • Dextrose/NaCl IV
  • Hydrocortisone (cortisol)
51
Q

Causes of acute adrenal insufficiency

A
  • lesions secondary to surgery
  • abrupt withdrawal of glucocorticoids (high dose/prolonged use)
52
Q

Symptoms of acute adrenal insufficiency

A

GIT symptoms, low Na+, high K+, weakness, lethargy, hypotension

53
Q

Common symptoms of Addison’s disease

A

hyperpigmentation, weight loss, weakness, fatigue, hypotension, inability to maintain fasting blood sugar

54
Q

Management of Addison’s disease

A
  • Hydrocortisone
  • Fludrocortisone acetate
55
Q

Indicator of adequate replacement therapy in chronic adrenal insufficiency

A
  • disappearance of hyperpigmentation and electrolyte imbalances
  • plasma ACTH levels monitored and urinary free cortisol, adjust dosage for stress
56
Q

Causes of Cushing’s syndrome

A
  • pituitary adenoma
  • tumour of the adrenal gland
57
Q

Symptoms of Cushing’s syndrome

A

round plethoric face, truncal obesity, muscle wasting, thinning purple striae, poor wound healing, osteoporosis

58
Q

Management of Cushing’s syndrome

A
  • Surgery
  • Hydrocortisone