Pharmacology - Endocrine Flashcards
Describe: Acromegaly
- Caused by excess production of growth hormone
- Most commonly affects middle-aged
- Can result in premature death
- Due to slow onset it is frequently incorrectly diagnosed
- Most common symptoms are abnormal growth of hands & feet.
Describe: Acromegaly Treatment
Aim is to reduce Growth Hormone production:
- Surgical removal of tumour, difficult due to tumour’s position within brain
- Drug therapy:
Ooctreotide & Lanreotide (somatostatin analogues, somatostatin receptor ligands SRLs)
Opegvisomant (growth hormone receptor antagonist)
Obromocriptine (dopamine agonist)
- Radiation therapy
Results of Deficit of Growth Hormone
Deficit:
- Dwarfism may be:
- general anterior pituitary dysfunction -
- specific GH deficit
- normal GH but hereditary somatomedin deficit
- Accelerated aging if loss of growth hormone occurs after adolescence
- decreased protein synthesis
Results of Excess of Growth Hormone
Excess GH
*Gigantism - early life pituitary tumour
*Acromegaly- pituitary tumour after adolescence
Dopamine agonists treat prolactinoma
Prolactin inhibiting factor (PIF) is dopamine
Dopamine acts at D2 receptors in the pituitary gland to inhibit prolactin release
Cabergoline and bromocriptine are dopamine agonists that inhibit prolactin production and can reduce the size of a prolactinoma
**Antipsychotics that are D2 receptor antagonists can cause hyperprolactinaemia
Hypopituitarism
- Rare - results from a deficiency in one or more pituitary hormones
- Panhypopituitarism – a deficiency in all anterior pituitary hormones
Multiple causes (acquired more often than congenital); tumours most common
+ traumatic, infective, vascular, autoimmune, functional (anorexia nervosa; starvation) - Symptoms mirror those of a primary deficiency in hormone secretion by the target endocrine gland
+ for example, primary and secondary hypothyroidism
+ if the deficiency is mild the patient may be asymptomatic - Managed by replacement therapy with the appropriate hormone(s)
+ e.g. recombinant GH (pituitary dwarfism); levothyroxine (2o hypothyroidism)
Describe: Hypelactinoma
Hyperlactinoma - too much prolactinoma in the blood
Benign pituitary tumours (adenomas) are the most common cause
Prolactin is the ‘milk hormone’
Common presentation:
Galactorrhoea - milky secretion from the breasts (male & female)
Amenorrhoea – females absence of periods
Hypogonadism – diminished production of sex hormones, diminished function of gonads in males & females
Erectile dysfunction - males
Vision loss, due to compression of the optic chiasm, is a common comorbidity
Explain the release and control of Growth Hormones
Hypothalamus release tropic factors into local circulation, & modified neurosecretory cells which release hormones enter the pituitary gland posterior,
The pituitary gland anterior releases primary hormones (such as prolactin & growth hormones), and trophic factors.
The GHRH (Growth Hormone Releasing hormone) stimulates the pituitary to release the GH (Growth Hormone), which is stopped by Somatostatin, a GH inhibitor.
TRH (Thyrotropin-releasing hormone) acts on the pituitary gland anterior, releasing TSH (Thyroid stimulating hormone), which acts on the Thyroid, causing the release of T3 (tri-iodothyroxine) & T4 (Thyroxine), both stimulate metabolic rate and growth, by acting at nuclear receptors to regulate gene transcription.
Describe both Hypersecretion & Hyposecretion, and the hormone whose activity results in these conditions.
Hypersecretion – too much hormones, resulting from an adenoma, a benign tumour
Hyposecretion – hormones are made against the hormone releasers, resulting from autoimmune disease.
GHRH activity results in these conditions.
The hypothalamic-pituitary axis
Hypothalamus releases TRH, causing the pituitary to release TRH onto the Thyroid, which releases T3 & T4, resulting in action within tissues. The negative feedback loop results in balance, loss of the feedback results in an unbalanced & diminished axis.
Thyroid hormone synthesis by follicle cells
TSH stimulates the Thyroid to synthesize Thyroid hormones, by stimulating iodide uptake into the cells by the transport protein Pendrin into the Follicle Lumen where TPO and TO enzymes catalyse addition of tyrosyl residues in Thyroglobulin.
When Thyroid hormones are needed the Thyroglobulin are Phagocytosed back into the cell and de-iodinated for more hormone synthesis.
Drugs act here to reduce the TPO action, limiting synthesis of Thyroid hormones.
Describe Hypothyroidism
Hypothyroidism – most common is autoimmune disease where antithyroid antibodies are made, stopping Thyroid hormone production.
A version called Hashimoto’s thyroiditis results in an enlarged thyroid gland.
Women may also get postpartum thyroiditis, but will typically recover.
May also occur from iodine deficiency.
Treated with lifelong hormone replacement.
Clinical signs & symptoms of hypothyroidism
Tiredness
Weight Gain
Cold intolerance
Goitre (large thyroid glands)
Dry thin hair
Dry skin
Mental Slowness
Slow heart rate
Slow-relaxing reflexes
Describe Hyperthyroidism (thyrotoxicosis)
Grave’s disease – autoimmune disease where antibodies act like TSH, meaning Thyroid hormones are released continuously, but can be caused by an inflammatory process or drug action.
Treated by antithyroid drugs, surgery or radiation.
Clinical features of hyperthyroidism (thyrotoxicosis) symptoms and signs
Weight Loss
Increase appetite
Tremor
Heat intolerance
Hyperkinesis
Overexcitable heart
Grave’s disease may result in bulging eyes
Hyperthyroidism treatment - 3
Treatment options:
1. Antithyroid drugs (e.g., Carbimazole): BetaBs may be coadministered for faster symptomatic relief.
2. Radioiodine: Only used for patients who have been made euthyroid first. It is contraindicated in pregnancy & breastfeeding.
3. Surgery: Reserved for patients who are euthyroid prior to the procedure.
Grave’s disease diagnosis
Graves’ disease is diagnosed with a low serum TSH & elevated T3 or T4 levels. TSH receptor antibodies are often present in cases, while thyroid peroxidase (TPO) & thyroglobulin antibodies are commonly found.
Q: What is Primary Hyperaldosteronism (Conn’s Syndrome)?
A condition caused by adrenal adenomas (benign tumours) producing excess aldosterone, leading to excessive sodium reabsorption and high blood pressure.
Q: What is the treatment for Primary Hyperaldosteronism (Conn’s Syndrome)?
A: Surgery to remove the adenoma or the use of aldosterone antagonists
Q: What is Hypoadrenalism (Addison’s Disease)?
A: A condition typically caused by autoimmune destruction of the adrenal glands, leading to insufficient production of cortisol and aldosterone.
Q: What is the treatment for Hypoadrenalism (Addison’s Disease)?
A: Hormone replacement therapy.
Q: What is Hypercortisolism (Cushing’s Syndrome)?
A: A condition caused by either endogenous (overactive adrenal glands or excess ACTH) or exogenous (glucocorticoid therapy for other conditions) factors, leading to excess cortisol production.
Q: What is the treatment for Hypercortisolism (Cushing’s Syndrome)?
A: Withdrawal of glucocorticoids or the use of cortisol synthesis inhibitors.
Q: Where is the adrenal gland located?
A: The adrenal gland is a triangular structure located on top of the kidneys.