Other endocrine conditions Flashcards
What is Diabetes Insipidus?
A lack of Anti-diuretic hormone (ADH, or Vasopressin)
What are the symptoms of Diabetes Insipidus?
Polyuria (> 2L/day) and Polydipsia
What treatments are available for Diabetes Insipidus?
Vasopressin injections, multiple dosage forms of Desmopressin
Where are the adrenal glands located?
Directly above both kidneys
What are the different regions of the Adrenal gland? (GFRI)
Zona glomerulosa, zona fasciculata, zona reticularis and the inner medulla
Where in the Adrenal gland is Aldosterone produced? (Salt)
Zona glomerulosa
Where in the Adrenal gland is Cortisol and other corticosteroids produced? (Sugar)
Zona fasciculata
Where in the Adrenal gland are Androgens produced? (Sex)
Zona reticularis
Where in the Adrenal gland is Epinephrine and Norepinephrine produced?
The inner medulla
What is the function of Aldosterone?
Promotes Na+ reabsorption in the kidney and increases K+ and H+ excretion in the urine
What is the function of Cortisol?
Helps the body adapt to stress, plays a role in metabolism to increase blood glucose concentration at the expense of protein and fat stores, has permissive actions on other hormones and has anti-inflammatory and immunosuppressive effects.
What effects does Cortisol have on the body during stress?
Immunosuppression (immune system), anti-inflammatory effects, gluconeogenesis (liver), protein catabolism (muscle) and lipolysis (adipose tissue).
Cortisol (think of what it does)
Glucocorticoid
Aldosterone (think of what it does)
Mineralcorticoid
What could be the cause of Aldosterone hypersecretion?
Adrenal adenoma causing hypersecretion, or high activity of Renin-angiotensin system
What could happen as a result of Aldosterone hypersecretion?
Hypernatremia, hypokalemia and resistant hypertension
What is the name of Cortisol hypersecretion?
Cushing’s Syndrome
What could be the cause of Cortisol hypersecretion?
Overstimulation of Adrenal gland via excess Corticotrophic-releasing hormone (CRH) and/or excess ACTH, or adrenal adenoma causing excess secretion.
What could happen as a result of Cortisol hypersecretion?
Glucose excess, protein shortage, abnormal fat distribution (moon-face), thin appendages due to muscle breakdown and poor wound healing due to inadequate protein formation
What treatments are available for Cortisol hypersecretion?
Metyrapone, Ketoconazole
What is a deficiency of Cortisol and Aldosterone known as?
Addison’s Disease
What treatments are available for a deficiency of Cortisol and Aldosterone?
Lifelong steroid treatment
Hydrocortisone - cortisol replacement
Fludrocortisone - aldosterone replacement
What three things are responsible for maintaining extracellular Ca2+ levels?
Parathyroid hormone (PTH), Calcitonin and Vitamin D
What is the impact of Hypocalcaemia? (Think opposite)
Increase in muscle/nerve excitability, which can lead to a spasm of muscles (potential for death via spasm of respiratory muscles)
What is the impact of Hypercalcaemia? (Think opposite)
Decreases muscle/nerve excitability, which can cause cardiac arrhythmias.
What is bone deposition?
The process whereby new bone is formed from osteoblasts
What is bone resorption?
The process where osteoclasts break down bone tissue
What does RANKL do?
Increases osteoclast differentiation and decreases osteoclast apoptosis, therefore increasing their number and promoting bone resorption in the long term. Ligand is referred to as RANKL.
What is OPG (osteoprotegrin)? (Think PROTECT)
Decoy receptor for RANKL. It decreases osteoclast numbers and promotes bone deposition over the long term.
What happens when plasma Ca2+ concentration falls?
PTH secretion is increased.
Describe the fast exchange of Ca2+ release from bone
PTH induces a rapid efflux of Ca2+ from the fluid in the canaliculi of the bone. PTH receptors on osteocytes and osteoblasts are GPCRs coupled to G alpha-S. An increase in cAMP causes Ca2+ to move into cells. Gap junctions allow Ca2+ movement through osteoblasts and into the plasma.
Describe the slow exchange of Ca2+ release from bone
Pathway is activated from prolonged hypocalcaemia. PTH activates osteoblasts to increase RANKL expression, therefore number of osteoclasts increases and apoptosis decreases. The osteoclasts increase bone resorption, which increases plasma Ca2+ concentration. Balance is restored when GIT absorption of calcium is increased.
How does PTH affect the kidneys?
PTH acts in the kidneys and causes an activation of Vitamin D, which causes an increase in Ca2+ absorption in the GIT. As well as this, it promotes the retention of Ca2+.
What is the purpose of Calcitonin?
Antagonistic hormone to PTH. It acts to decrease the extracellular/plasma levels of Ca2+ by decreasing the movement of Ca2+ from the canaliculi in the bone, inhibits osteoclast activity and inhibits the reabsorption of Ca2+ in the kidney (excretion increases).
How does Vitamin D become active in the body?
It is activated in the liver by adding an OH group, and is stored until required. Then, in the kidney, a second OH group is added by PTH.
What does Vitamin D do in the body?
It acts at nuclear receptors which promotes gene expression. The expressed genes lead to increased absorption of Ca2+ in the GIT, which increases plasma Ca2+ levels and restores the balance.
What is bone remodelling?
A process where old bone is replaced by new bone, involving osteoclasts and osteoblasts.
What do osteoBlasts do?
They fill (BUILD) in bone cavities with bone matrix and release cytokines to attract osteoclasts.
What do osteoClasts do?
They release proteases that dissolve bone mineral matrix and CLEARS damaged bone. It also releases chemicals that attracts osteoblasts.
What cytokines help control bone remodelling?
IL-1, IL-6, TNF and granulocyte colony stimulating factor (GCSF)
What environmental risk factors are there for developing osteoporosis?
Low calcium in diet, low vitamin D intake/lack of sunlight exposure, physical inactivity, alcohol, smoking, thin body type
What is Osteoporosis?
A systemic skeletal disease characterised by decreasing bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture.
What is used to diagnose/detect Osteoporosis?
A Dual Energy X-ray Absorbimetry (DEXA) scan
What is primary Osteoporosis?
The most common form, where a patient has no other disorders known to cause osteoporosis. For example: post-menopausal osteoporosis.
What is secondary Osteoporosis?
Osteoporosis that is related to: Anorexia, IBD, Endocrine conditions (Type 1 DM, Cushing’s syndrome, Hyperthyroidism), Rheumatoid arthritis and use of drug therapy (steroid induced, or Carbamazepine, Phenytoin, Heparin, Furosemide, PPIs, Cyclosporin).
How do Steroids contribute to the risk of developing secondary Osteoporosis?
Steroids decrease osteoblast activity and lifespan, decrease Ca2+ absorption from the GIT and increase renal calcium loss causing abnormal PTH and vitamin D activity and suppress sex hormones.
What is Menopause?
Menopause is the permanent cessation of menstruation resulting from a loss of activity in the ovarian follicles.
When can a diagnosis of Menopause be determined?
After a period of 12 months of amenorrhea.
What is amenorrhea?
An absence of a menstrual period.
What is the menopausal pattern, with respect to hormones?
Low Oestrogen, High LH and FSH
What is premature menopause characterised by?
Menopause that occurs before the age of 40.
What are the short term symptoms of Menopause?
Shortening or lengthening of menstrual cycle, menstrual blood loss is altered, vasomotor symptoms (hot flushes, night sweats, palpitations), psychological problems, musculoskeletal symptoms, vaginal symptoms and urinary symptoms.
What are the long term symptoms of Menopause?
Loss of calcium from bones gives rise to increase fracture risk via osteoporosis and changes in blood lipid profile giving an increased risk of CVD. These signs may be characterised by fractured NOF, MI or a stroke.
What is forward curvature of the spine called?
Kyphosis
What is the condition prior to Osteoporosis called?
Osteopenia
Who are most at risk of developing Osteoporosis?
Postmenopausal women, people with low BMI (>19), conditions that affect bone metabolism (IBD, Hyperthyroidism, Rheumatoid Arthritis), excess smoking and alcohol, patients using long-term steroid
What is recommended for those at low risk of developing Osteoporosis according to the NOGG guidelines?
Lifestyle changes and Vitamin D/Calcium
What is recommended for those at medium risk of developing Osteoporosis according to the NOGG guidelines?
Assess BMD with DEXA scan
What is recommended for those at high risk of developing Osteoporosis according to the NOGG guidelines?
Consider starting treatment without BMD assessment
How is a person’s risk of developing Osteoporosis assessed?
Fracture Risk Assessment Tool (FRAX)
What lifestyle changes might be recommended to reduce the risk of Osteoporosis?
Exercise (Walking regularly), avoiding smoking and moderation of alcohol intake
What should be offered if dietary intake of Calcium and Vitamin D is sub-optimal?
1000mg of Calcium and 800 UI of Vitamin D per day
What is first-line for Osteoporosis?
A Bisphosphonate
What is second-line for Osteoporosis?
Denosumab, Raloxifene, Teriparatide, Strontium ranelate, Romosozumab or HRT
What is the mechanism of action of the Bisphosphonates?
They are absorbed into the hydroxyapatite crystals in the bone, it then slows the rate of their growth and dissolution which decreases the rate of bone turnover.
Name some Bisphosphonates.
Alendronic Acid, Zoledronic Acid, Risedronate, Ibandronic Acid
What counselling points might you mention for Bisphosphonate treatment?
Take on an empty stomach, swallow tablet whole and don’t crush it, take whilst sitting upright, remain upright for 30-60 mins afterwards
What are the important side effects that a patient should be aware of with Bisphosphonate treatment?
Osteonecrosis of the jaw, atypical femoral fractures, osteonecrosis of auditory canal
What is first-line in STEROID-INDUCED OSTEOPOROSIS?
Alendronic Acid or Risedronate
What levels of Vitamin D is classed as a deficiency?
Less than 25 nmol/L
What is the treatment of Vitamin D deficiency?
Loading dose: 50,000 units once weekly for 6 weeks, 40,000 once weekly for 7 weeks, 4000 units daily for 10 weeks
Maintenance dose: 800-2000 units daily to start 1 month after LD completed
What is the mechanism of action of DenosuMAB?
Monoclonal antibody to RANKL, inhibits binding of RANKL to RANK.
What is the mechanism of action of Raloxifene?
It is a selective oestrogen receptor modulator, and has mixed agonistic/antagonist actions at oestrogen receptors. It stimulates osteoblast activity and inhibits osteoclast activity.
What is the mechanism of action of Teriparatide?
It is an active fragment of PTH, acts at PTH receptors and has opposite effects to PTH.
What is the mechanism of action of Strontium?
Increases bone deposition by osteoblasts, and also decreases bone resorption by osteoclasts. It does this by increasing osteoclast apoptosis. Known as a ‘dual action bone agent’.
What HRT treatment is offered to a female with an intact uterus?
Oestrogen AND Progestogen treatment
What HRT treatment is offered to a female without an intact uterus?
Oestrogen ONLY treatment
Why is only Oestrogen given to women without an intact uterus?
Because if there is no uterus, there is no endometrium to stimulate.
Why are both Oestrogen AND Progestogen given to women with an intact uterus?
To prevent over-stimulation of the endometrium by unopposed oestrogen.
What is the aim of Oestrogen therapy?
It aims to restore and maintain near normal levels of Oestrogen. It reinstates the negative feedback loop to allow FSH and LH levels to fall.
What is the difference between HRT and contraceptive oestrogens?
HRT is a lot less potent than the synthetic oestrogens used in contraceptives, meaning that HRT cannot be used as a form of oral contraceptive.
Name the more androgenic progestogens.
Norethisterone and Levonorgestrel
Name the less androgenic progestogens.
Dydrogesterone and Medroxyprogesterone acetate
Name the different routes of HRT available.
Oral, Transdermal (Patch, Gel, Spray), Vaginal (Cream, Vaginal ring), Implant
Explain why the transdermal route might be better than the oral route for HRT
The transdermal route gives less day-to-day variation in blood plasma hormone levels. It produces a natural, physiological oestradiol:oestrone ratio. It also bypasses the first layer of metabolism and has less effect on clotting factors produced in the liver. As as result, there is a lower risk of VTE.
Why is an annual review important in HRT?
To assess whether there is a risk of stroke, breast cancer, endometrial cancer and VTE.
What are the symptoms of Oestrogen HRT?
Nausea and vomiting, abdominal cramps and bloating, weight gain, breast tenderness and enlargement, premenstrual-like syndrome, sodium and fluid retention
What are the symptoms of less androgenic Progestogen?
Abdominal bloating, mood changes (irritability and depression), breast tenderness
What are the symptoms of more androgenic Progestogen?
Greasy skin and hair and it can offset the protective effect of oestrogens on lipid profile.
What are the benefits of HRT (short term)?
Control of symptoms of peri/post menopause (hot flushes and sweats, headaches, urinary and vaginal symptoms, mood changes and loss of libido, thin skin, brittle nails, hair loss, generalised aches and pains).
What are the benefits of HRT (long term)?
Decreased risk of osteoporosis. The oestrogen rebalances bone resorption and formation therefore stopping bone loss.
What are the risks of HRT?
VTE, Breast cancer, Endometrial cancer, Ovarian cancer, Stroke and CHD.
What is Tibolone used for?
Short term treatment of menopausal treatments, prophylaxis of osteoporosis/endometriosis
What is Clonidine used for?
Treatment of vasomotor symptoms (hot flushes) in menopause.
What other remedies can be used for menopause symptoms?
St John’s Wort and products containing phytoestrogens (Black Cohosh, Red Clover).
What risks are associated with other menopausal symptomatic treatment?
St John’s Wort - CYP3A4 inducer
Liver impairment with Black cohosh
Red clover contains coumarins, interacts with warfarin
What treatments are available for Male Pattern Baldness?
Minoxidil and Finasteride
What is the mechanism of action of Finasteride?
It is a 5-alpha reductase inhibitor that blocks the conversion of testosterone into dihydrotestosterone. Too much dihydrotestosterone will shrink hair follicles causing faster hair loss.
What diseases of the prostate are prevalent in men?
Prostate cancer, Benign prostatic hyperplasia (BPH), Prostatitis
What are the symptoms of BPH?
Impeded urine flow (dribbling), Prostate-specific antigen presence
What are the different levels of the International Prostate Symptom Score (IPSS)?
1-7 - Mild (‘Watchful waiting’ only at this stage)
8-19 - Moderate
20-35 - Severe
What treatments are available for BPH?
‘Watchful waiting’, surgical options, Drug treatment (Tamsulosin and Finasteride)
What treatments are available for Erectile Dysfunction?
Vacuum devices, Injections (Caverject), Oral testosterone, Phosphodiesterase type-5 inhibitors (Sildenafil, Tadalafil, Vardenafil)
How do phosphodiesterase-5 inhibitors work?
They prevent the breakdown of cyclic guanosine monophosphate (cGMP), which sustains an erection.
What is the risk of phosphodiesterase inhibitors?
Risk of severe HYPOtension
What is the cause of primary GH deficiency?
A pituitary defect (anterior)
What is the cause of secondary GH deficiency?
A hypothalamic dysfunction - lack of GHRH or IGF (insulin-like growth factor)
What treatment is available for GH deficiency?
Somatotropin (recombinant GH)
What is the cause of GH excess?
It is most often due to a benign tumour in somatotrophs (the cells that release GH in the anterior pituitary)
What is GH excess called in children?
Gigantism. Leads to massive height growth into adulthood, possibility for >8ft.
What is GH excess called in adults?
Acromegaly. It leads to thicker bones, more soft tissue proliferation, bone thickening in the face and extremities and peripheral nerve disorders.
What treatments are available for GH excess?
Surgery, Somatostatin analogues and IGF inhibitors.
What drugs are available for GH excess?
Octreotide, Lanreotide, Pasireotide (mimic Somatostatin)
Pegvisomant (IGF inhibitor, highly selective antagonist of GH)
What are the side effects associated with long-term corticosteroid use?
Adrenal suppression, immunosuppression, secondary osteoporosis, psychotic reactions (suicidal thoughts, euphoria, nightmares, insomnia), Diabetes, Cushing’s Syndrome
