Week 6 Flashcards
Hypothalamus Dysfunction
- The hypothalamus plays a central role in maintaining homeostasis by regulating endocrine, autonomic, behavioural, and circadian functions.
- It is composed if discrete nuclei, each with distinct physiological responsibilities.
- Hypothalamic dysfunction can arise from diverse structural, genetic, inflammatory, infectious, metabolic, and iatrogenic causes.
- Damage or impairment to any of these hypothalamic nuclei disrupts specific neuroendocrine or autonomic pathways, leading to characteristic clinical syndromes.
Hypothalamus dysfunction aetiology
Hypothalamic nuclei can be impaired by a variety of structural and non-structural insults, including:
- Intracranial masses: e.g. craniopharyngiomas, chordoid gliomas, hypothalamic hamartomas.
- Vascular events: ischemic stroke, aneurysmal subarachnoid haemorrhage.
- Trauma or surgery: especially involving the lamina terminalis or third ventricular region.
- Medications: particularly dopamine antagonists (e.g. antipsychotics), which may disrupt dopaminergic inhibition of prolactin and GnRH.
- Inflammatory and infectious processes: such as tuberculous meningitis, neurosarcoidosis or multiple sclerosis
Hypothalamus dysfunction Clinical man
A patient’s clinical manifestations will be diverse depending on where the dysfunction is in the hypothalamus
Hypopituitarism what is it
This refers to decreased secretion of pituitary hormones, which can result from either:
1) Diseases of the pituitary gland.
Or
2) Diseases of the hypothalamus = diminished secretion of hypothalamic-releasing hormones and secretion of corresponding pituitary hormones.
Hypopituitarism aetiology
- Hypothalamus disorders (read info from page).
- Pituitary disorders: impair secretion of one or more hormones commonly due to mass lesions (e.g. adenoma), infarction (e.g. from Sheehan’s Syndrome) or iatrogenic (e.g. from pituitary adenoma surgery, radiation), bleeding (e.g. due to adenoma) or infections (more likely in immunocompromised patients). These conditions commonly lead to hypopituitarism – partial or complete deficiency of anterior and/or posterior hormones.
Hypopituitarism clinical man
- Depend upon the cause as well as the type and degree of hormonal insufficiency.
- Patients may be asymptomatic or present with symptoms related to hormone deficiency or a mass lesion, or nonspecific symptoms such as fatigue.
Growth hormone deficiency Aetiology
Aetiology:
The causes of GH deficiency are the same as the causes of deficiencies of other pituitary hormones, for example:
- Pituitary tumour or the consequences of treatment of the tumour, including surgery and/or radiation therapy.
- Extrapituitary tumour (e.g. craniopharyngioma).
- Idiopathic.
- Sarcoidosis.
- Sheehan syndrome (excessive blood loss during or after delivery of a baby may affect the function of the pituitary gland, leading to a form of maternal hypopituitarism).
The causes of GH excess are:
- Somatotroph adenoma of anterior pituitary.
- Less common: excess secretion of GH-releasing hormone by hypothalamic tumours or neuroendocrine tumours.
GH Deficiency clinical man
In children:
- Shunted growth: the most noticeable effect is reduced growth rate, leading to shorter stature compared to peers.
- Delayed puberty: children may experience delayed onset of puberty, affecting their physical development.
- Facial features: growth hormone deficiency can result in immature facial features, such as a prominent forehead and a flat nasal bridge.
In adults:
- Reduced muscle mass: adults with GH deficiency may experience a decrease in muscle mass and strength.
- Increased fat levels: there may be an increase in body fat, particularly around the abdomen.
- Metabolic disturbances: GH deficiency can lead to various metabolic issues, including changes in lipid metabolism and insulin sensitivity leading to dyslipidaemia, increased inflammatory markers, and an increased in biochemical markers of endothelial dysfunction.
Hypersecretion of GH
Stimulation of growth of many tissues, such as skin, connective tissue, cartilage, bone, viscera, and many epithelial tissues.
In children:
- Gigantism: excess GH leads to excessive growth and height, often resulting in gigantism if it occurs before the closure of growth plates.
- Facial changes: children may develop characteristic facial features, including an enlarged jaw and forehead.
In adults:
- Acromegaly: in adults. GH excess results in acromegaly, characterised by the enlargement of bones and tissues. Particularly in the hands, feet, and face.
- Organ enlargement: there can be an increase in the size of internal organs, leading to complications like hypertension and diabetes.
- Symptoms of fatigue and general weakness.
- Common clinical comorbidities; sleep apnoea, cardiovascular dysfunction, neuropathy, hypogonadism, hyperglycaemia or a combination.
Primary Adrenal Insuffciency what is it
Addisons disease
a rare condition where the adrenal glands don’t produce enough cortisol and aldosterone
Primary Adrenal Insuffciency Aetiology
- Autoimmune adrenalitis (most common) – autoimmune process that destroys the adrenal cortex; evidence of both humoral and cell-mediated immune mechanisms directed at adrenal cortex.
- Infectious causes (e.g. Tuberculosis can destroy glands, HIV/AIDS (with opportunistic infections), fungal infections, bacterial sepsis adrenal haemorrhage).
- Infiltrative or metastatic disease (e.g. lung, breast, melanoma, lymphoma).
- Haemorrhagic/infarction (e.g. anticoagulation, trauma, sepsis).
- Genetic.
- Drugs.
Primary Adrenal Insuffciency Epidemiology
- Primary adrenal insufficiency is a rare condition. This affects approximately 2,500 Australians, with 100 new diagnoses made each year. In primary adrenal insufficiency, the levels of all corticosteroid hormones are affected
Secondary adrenal insufficiency
Problem is in the pituitary gland (decreased ACTH). Aldosterone is preserved
Tertiary Adrenal Insufficiency
The problem is in the hypothalamus (decreased CRH) or functional suppression of the hypothalamic-pituitary-adrenal (HPA) axis
Tertiary Adrenal Insufficiency Aetiology
- Most common – exogenous glucocorticoids.
- Long-term steroid therapy (oral, inhaled, topical, intra-articular).
- Abrupt cessation of steroids without tapering.
- Hypothalamic tumours or trauma
Clinical Man of Primary Adrenal Insufficiency
- fatigue, weakness, nausea, weight loss, chronic hypotension, hypoglycaemia
- develop slowly overtime
- ## addisons crisis = hypoadrenal state
Cushing syndrome what is it
Primarily characterised by elevated cortisol levels in the blood, which can arise from various causes, including both exogenous and endogenous factors
Cushing syndrome Aetiology
- Exogenous Cushing Syndrome: this occurs when cortisol is introduced from outside the body, commonly through long-term use of steroid medications. This is called Iatrogenic Cushing Syndrome and is common in high income countries where medications are often prescribed for conditions like asthma or rheumatoid arthritis due to their structural similarity to cortisol.
- Endogenous Cushing Syndrome: this type results from the body producing excess cortisol. The most prevalent cause is a pituitary adenoma that secretes excess adrenocorticotrophic hormone (ACTH), leading to increased cortisol production from the adrenal glands. This specific condition is referred to as Cushing disease
Cushing syndrome Pathogenesis
- The pathogenesis of Cushing syndrome involves the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.
- Normally, the hypothalamus releases corticotropin-releasing hormone (CRH), stimulating the pituitary gland to secrete ACTH, which in turn prompts the adrenal glands to produce cortisol.
- In Cushing syndrome, this regulatory mechanism is disrupted, leading to abnormally high cortisol levels, regardless of whether the source is endogenous or exogenous
Cushing syndrome clinical man
The clinical manifestations of Cushing syndrome are directly related to the effects of excess cortisol on various tissues.
- Muscle wasting: due to increased breakdown of muscle tissue.
- Skin changes: thinning of the skin, easy bruising, and abdominal striae (stretch marks).
- Bone health: increased risk of fractures due to osteoporosis
Cushing syndrome and Addisons
C
CAUSE - autoimmmune destruction of the adrenal cortex, infections, hemorrhage, medications
HORMONE - decrease cortisol, aldosterone, androgens
CLINICAL - fatigue, weakness, weight loss, vomitting, hyperpigmentation
A
CAUSE - prolonged exposure to excess cortisol
EXO - exo steroids
ENDO- pituitary adenoma, adrenal tumor, ectopic ACTH
HORMONES - increased cortisol
Hypothyroidism what is it
a condition where the thyroid gland doesn’t produce enough thyroid hormones, leading to a slowdown in the body’s metabolism
Hypothyroidism Aetiology
- The overwhelming majority of patients who have hypothyroidism have thyroid disease (primary hypothyroidism). Primary hypothyroidism is due to inadequate production of thyroid hormone caused by disease of the thyroid gland.
- Central hypothyroidism is ore rare and refers to thyroid hormone deficiency due to a disorder of the pituitary, hypothalamus, or hypothalamic-pituitary portal circulation, resulting in diminished thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH) or both
Hyperthyroidism what is it
The overproduction of thyroid hormones
