Endocrine Flashcards
What pharmacological agents are used to treat obesity?
What is their mode of action?
Phentermine (Duromine) - a sympathomimetic amine with anorexic activity and appetite suppression effect through the hypothalamus. Given as 3 month therapy.
Orlistat - lipase inhibitor that causes steatorrhoea (reversible long-acting gastrointestinal inhibitor of lipases, which are required for systemic absorption of dietary triglycerides)
Off label use of agents that also cause weight loss-
Non diabetics: Topiramate (monosaccharide antiepileptic med, also used in migraine. SE teratogenic)
Diabetics: Exenatide (GLP1 agonist), Liraglutide (Victoza / GLP1 analogue)
What are the neurotransmitters that cause:
- satiety
- hunger
Satiety caused by:
- (gut) - cholecystokinin, GLP-1, oxyntomodulin, PYY3-36
- (adipocytes) - leptin
- (pancreas) - insulin, amylin, pancreatic polypeptide
Hunger stimulated by grehlin (from stomach)
(PEP lecture)
What are the HbA1c targets for adult T2DM in:
1. General population
2. Newly diagnosed DM with no CV disease
3. Longer duration DM or those with CV disease
4. Recurrent severe hypoglycaemia or Hypoglycaemia unawareness
5. Patients with major comorbidities likely to limit life expectancy
- = Or
Where are Calcium sensing receptors found in the body and what do they do?
What disease process is affected by CaSR?
(PEP lecture)
CaSR’s are expressed in the:
- parathyroid gland
- renal tubules
- (less important) thyroid C cells, osteoblasts, osteoclasts, breast, intestine, brain
CaSR is a G-coupled membrane protein that responds to changes in serum calcium and Amino acid levels.
Function in
Parathyroids - regulates PTH secretion. Normally causes a tonic INHIBITORY action on PTH secretion. It prevents release of PTH when Ca is high.
(when Ca level falls, the parathyroid gland is “released from tonic inhibition” –> PTH secretion)
Renal tubules - promotes Calciuria when Ca is high.
In Prox tubule- inhibits phosphaturic action of PTH
In LoH- inhibits salt reabsorption
In Dist tubule- inhibits Ca reabsorption
In Coll tubule- inhibits ADH action
FAMILIAL HYPOCALCIURIC HYPERCALCEMIA occurs when there is an inactivating mutation of CaSR which renders it less sensitive to rises in Ca (raises set point to tolerate abnormally high levels of serum Ca)
How do you diagnose Familial Hypocalciuric Hypocalcaemia?
URINARY CALCIUM shows relative hypocalciuria!! Urine Ca is inappropriately normal in the context of Hypercalcaemia. (Inappropriate increase in renal tubular reabsorption of calcium, when it should be excreting it in the urine)
Other findings: Hypercalcaemia Normal PTH Normal PO4 Vit D / Calcitriol normal or elevated Mg normal or elevated Renal function normal
What is the mechanism behind Autosomal dominant Hypocalcaemia?
What are the biochemical findings?
Autosomal dominant Hypocalcaemia - lowers the “set point” and renders the CaSR more sensitive Ca.
Hypocalcaemia High Urine calcium PTH normal Mg normal Recurrent nephrolithiasis
What is the mechanism of Cinecalcet?
CINECALCET DECREASES PTH.
(“CINNA brings down PANEM in THE Hungergames!!” = CINNAcalcet brings down PTH)
Binds to CaSR and increases the sensitivity of the CaSR to calcium –> reduces PTH secretion –> reduces plasma PTH.
Used to treat primary and secondary hyperparathyroidism.
Side effects:
GI side effects
Hypocalcaemia (unlike Calcitriol) - easy to treat with CaPO4 or Calcitriol
What is the clinical profile of asymptomatic primary hyperparathyroidism?
Middle aged/ elderly Mild Hypercalcaemia Normal or mildly increased PTH Normal renal function, urine Ca Normal Vit D Normal BMD
DDx: thiazides, lithium, FHH
What is the best management for patients with asymptomatic primary hyperparathyroidism?
(PEP lecture)
Surgery may be appropriate in the majority of patients with asymptomatic primary hyperparathyroidism, due to:
- improvement in BMD (note BMD usually declines at 10 yrs, more significant in cortical bone in radius/NOF than trabecular bone in Lspine)
- reduction in fractures
- reduced frequency of kidney stones
- improvements in some Neuro-cognitive elements
Surgery appropriate if:
- Ca > 0.25 mmol/L above the upper limit of normal
- eGFR < 60
- Osteoporosis on BMD a (T score <2.5) or previous min trauma #
- age under 50
If patient does not qualify for surgery,
- Monitor closely with annual Ca and Creatinine
- Bisphosphonates/ antiresorptive therapy stabilises BMD a but does not cure Hypercalcaemia or lower PTH
- Calcimimetics decrease Ca but NO EFFECT ON BMD
- BMD every 1-2 years
What are the causes of PTHrP-related Hypercalcaemia (Hypercalcaemia of malignancy)?
Squamous cell carcinoma (lung, head/neck, Oesophageal, cervical) Breast Renal Ovaries Pancreas Prostate T-cell lymphoma
Hereditary Vitamin D resistance syndromes.
What is the difference between VDDR type 1 and 2?
(PEP lecture)
Features of VDDR type 1: (Due to defect/lack of 1-Alpha Hydroxylase enzyme in the kidney --> unable to convert 25-OH Vit D to 1-25-OH Vit D) No alopecia Osteomalacia Hypocalcaemia Secondary hyperparathyroidism LOW 1-25-OH vitamin D
Features of VDDR type 2: (Due to a defect in the Vit D receptor in nucleus, which is unable to bind 1-25-OH Vit D) Osteomalacia Alopecia Hypocalcaemia Secondary hyperparathyroidism Normal 25-Vit D HIGH 1-25-OH Vit D
Describe the conversion of 25-OH Vit D to 1,25-OH Vit D in the renal tubules.
Contrast what stimulates and inhibits this reaction.
1-ALPHA HYDROXYLASE is the enzyme in the renal tubule that converts 25-OH Vit D to 1,25-OH Vit D.
1-alpha Hydroxylase is STIMULATED by:
- PTH
- Low Ca
- Low PO4
- Low FGF23
1-alpha Hydroxylase is INHIBITED by:
- 1,25-OH Vit D (negative feedback on itself)
- High Ca
- High PO4
- High FGF23
What are the extra-renal cells with 1alpha Hydroxylase activity?
How is this enzyme regulated?
1-alpha Hydroxylase enzyme converting 25-OH Vit D to 1,25-OH Vit D is present in:
- macrophages
- keratinocytes
- hair follicles
- cardiac myocytes
But the regulation of 1-alpha hydroxylase in non-renal tissue is
- NOT stimulated by PTH (as no PTH receptors)
- NOT inhibited by FGF23
- inhibited by corticosteroids (hence can use steroids in sarcoidosis)
- stimulated by gamma interferon, TNF alpha and IL2
What are the causes of Hypercalcaemia associated with elevated 1,25 OH Vit D?
SARCOIDOSIS most common
Other granulomatous disease : Wegeners, acute granulomatous pneumonia, talc or silicone granulomatosis
Cat scratch fever
Crohns
What are the target serum 25-OH Vit D levels for:
- End of winter
- Summer
- Falls prevention
- Fracture prevention
- End of winter >50 mmol/L
- Summer >60
- Falls prevention > 60
- Fracture prevention > 75
Describe the regulation of PO4 in the renal tubules
PO4 is reabsorbed against the electrochemical gradient in Prox tubules via the Na-phosphate transporter NPT2a.
Regulation of NPT2a:
Low PO4 –> causes insertion of NPT2a into plasma membrane of Prox tubular cells –> increases Po4 reabsorption
High PO4 –> INCREASES SERUM FGF23 –> rapid internalisation and lysosomal destruction of NPT2a –> reduces PO4 reabsorption
What is FGF23?
HIGH SERUM PO4 INCREASES FGF23!!!
–> FGF23 acts to lower PO4.
(“PHOtos increase my FIGure!…Please stop, I’m NOT PHOTOGENIC TODAY (NPT)” = PHOSPHATE increases FGF23 which reduces NPT2a)
FIbroblast growth factor 23 REGULATES PHOSPHATE HOMEOSTASIS.
- Rises in response to HIGH serum phosphate
- Decreases NPT2a expression
- Decreases 1,25 OH Vit D
- Acts independently of PTH
- Is inactivated by PHEX endopeptidase
FGF23 has 2 mechanisms to lower PO4:
- -> FGF23 DECREASES NPT2a (sodium-phosphate transporter) EXPRESSION in the proximal tubule.
- -> DECREASED PO4 reabsorption
- -> LOWERS SERUM PO4
AND…
- -> FGF23 DECREASES 1,25OH Vit D
- -> DECREASED PO4 absorption
- -> LOWERS SERUM PO4
ALSO simultaneously, as a physiological response to a high serum PO4 (independent of FGF23)
PTH IS INCREASED.
( due to
- direct stimulation of PTH secretion, and
- indirectly, as a result of reduced serum Calcium
- ** Osteocytes secrete FGF23 (ie a bone derived hormone!)
- inhibition of 1-alpha Hydroxylase enzyme activity)
What is the body’s physiological response to a LOW serum phosphate?
Decreases FGF23 –> enhances expression of NPT2a –> increased PO4 reabsorption at the renal tubule
Increases 1,25 OH Vit D synthesis
- -> increased intestinal absorption of Ca and PO4
- -> increased release of Ca and PO4 from bones
- -> increased renal reabsorption of Ca and PO4
What are the conditions associated with increased FGF
23?
(PEP lecture)
3 conditions: all are Hypophosphataemic rickets disease
- AUTO DOMINANT HYPOPHOSPHATAEMIC RICKETS
Mutation that results in decreased cleavage/degradation of FGF23 - X-LINKED HYPOPHOSPHATAEMIC RICKETS
Loss of function mutation in PHEX gene –> decreased cleavage/degradation of FGF23 –> renal PO4 wasting –> rickets in age 2-3 - ONCOGENIC OSTEOMALACIA
Increased Tumour production of FGF23.
Tumours are usually small benign MESENCHYMAL TUMOURS.
Oat cell carcinoma, Sclerosing haemangioma, Fibromas.
Localisation: Whole body MRI, Octreotide scan, PET, or (***most useful) Gallium-Octreotide scan
What is the association with Ca supplements and risk of Cardiovascular events?
There is NO increased risk of cardiovascular events in patients on Ca and Vit D.
Ca supplements should only be used when dietary Ca intake can not be achieved. Food remains the best source of calcium.
Elderly people and patients with renal impairment who take Ca supplements “may” be at higher risk of CVD but there is no need to discontinue their use- just limit to low dose 500-600mg Ca a day
What are the Anti-resorptive drugs used for Osteoporosis?
- HRT, Tibolone
- prevents bone loss and reduces fracture risk in newly-postmenopausal women who are symptomatic from menopause
- but HRT increases risk of BREAST Ca, PE, Stroke, HTN - SERMS- Raloxifene
- used in older postmenopausal women but only reduces VERTEBRAL fractures
- ** DOES NOT PREVENT NON-VERTEBRAL fractures
- REDUCES risk of breast cancer (Tamoxifen used as Rx for BrCa!)
- can cause leg cramps and increase hot flushes
- best used in older women with low SPINAL BMD who have a FHx of BrCa - Bisphosphonates
- Aledronate oral, good for primary and secondary prevention of fractures in postmenopausal OP, particularly vertebral fractures,
plus good effect in non-vertebral, hip and wrist #s as well.
- Risedronate also good and reduces risk of fractures by about 40% (to a less extent in wrist)
- need proper compliance (if taken < half the time, not much effect)
- if not compliant, give IV Zoledronic acid, NNT 13 to prevent #s and also IMPROVES MORTALITY!!!
- SE of ONJ, usually in IV bisphosphonate in setting of cancer. Rare in oral bisphosphonates. ***ATRIAL FIBRILLATION with Zoledronic acid. - Denosumab (RANK-L antibody)
- also used in metastatic breast and castrate-resistant prostate cancer
- subcut mab given 6-monthly
- inhibits osteoclast formation and survival
- oestrogen opposes RANKL hence at menopause when there is less oestrogen, there is more bone remodelling and bone resorption
- note the effect on BMD is completely and rapidly reversible- BMD gets worse when treatment discontinued but can regain BMD a quicker if treatment restarted. But no actual evidence of increased fracture risk after drug is stopped.
- SE of ONJ
* ** RANK receptor is expressed on OSTEOCLASTS and causes activation of osteoclasts.
* ** Osteoprotegerin binds to RANKL as a decoy receptor & prevents it binding to RANK receptor. - Strontium ranelate
- makes bone matrix tougher because Strontium replaces Calcium in the bones - actual effect on cells is minimal
- ** INCREASES RISK OF AMI!!!
- NOT an anabolic drug, does not build bone
- reduces vertebral, non-vert and hip fractures in severe OP (T-score -3.0)
- reduces hip/non-vert fractures in women age > 80
- a second-line drug, only use if bisphosphonate not suitable as long as patient is low risk for CVD
- approved for men
- NOT approved for glucocorticoid-induced OP
What are the ANABOLIC agents available for Osteoporosis?
What is the criteria for starting on drug?
The only drug that effectively BUILDS new bone is Teriparatide, a daily SC injection for 18 months
- synthetic PTH given intermittently
- increases bone formation
- increases cortical bone and trabecular bone mass
- reduces vertebral and non-vertebral fracture
- NO data on hip fractures
- osteogenic sarcoma in rats only, but must warn patient of this rare s/e
Restricted to patients who satisfy the CRITERIA FOR TERIPARATIDE:
- severe OP with T-score < -3.0
- 2 MTF’s
- one fracture occurring whilst on 12 months bisphosphonate therapy, or intolerance to oral/IV bisphosphonatesz
What are the causes of atypical femoral fractures in the setting of a patient on treatment for Osteoporosis?
Atypical fractures of the femoral diaphysis are controversially related to bisphosphonates.
Criteria for diagnosis:
- subtrochanteric and diaphysea regions
- transverse or minimally oblique, chalk-stick fracture with medial spike, not comminuted. Looks like a stress fracture.
Controversial whether it is related to Bisphosphonates, but:
- ask about prodromal thigh or groin pain in anyone on long term bisphosphonates
- do an XR or Bone Scan to look for hotspots mid-shaft- may need surgery
- cease bisphosphonate - seems to improve bony changes
- Occurs in 1:1000 to 1:10,000 patients
What are the risk factors for developing Anti-resorptive Osteonecrosis of the jaw (ARONJ)?
Age older than 65 Periodontal disease Bisphosphonate > 2 years Smoking Dentures (surprisingly) Diabetes Invasive bone procedures such as tooth extractions
**If dental extraction required, no need to stop bisphosphonate, as ONJ is so rare and the benefits of antiresorptive agents far outweigh the small risk of ONJ a
** low serum CTX a bone resorptive marker is NOT predictive of ONJ
How long to use bisphosphonates?
If FEMORAL NECK t-score is < -2.5 after 3-5 years of therapy, should continue treatment.
Vertebral BMD continues to improve but Hip BMD a worse
If BMD is > -2.5 after 3-5 years it is reasonable to have a drug holiday but still need to measure BMD every 2 years
When should you start a bisphosphonate in someone who is on long-term glucocorticoids?
Patient on steroid for > 3 months And On a dose > 5mg a day And t score < -1.0
Can use Aledronate, Risedronate, or IV Zoledronic acid
(eTG)
What tests would you order to diagnose Acromegaly?
Failure of GH to suppress with a glucose load
Raised IGF-1
What is the Mx for Acromegaly?
Surgery (trans-sphenoidal microadenectomy if small tumour, total hypophysectomy if large)
+/- radiotherapy
Somatostatin analogue (OCTREOTIDE / PASREOTIDE / Lantreotide) - Pasreotide is a NEW somatostatin analogue, also used in Cushings, offers higher binding to 4 out of 5 somatostatin receptors, longer Half life, offers IGF-1 normalisation in 65% and reduced tumour volume
Possible role for adjunctive dopaminergic drug (BROMOCRIPTINE or CABERGOLINE)
PEGVISOMANT, a GH receptor antagonist
3rd line agent, very expensive, daily injection
What is Pseudo Cushings?
Where the Dynamics of Cortisol are altered and the levels may be high.
Associated with:
depression
Alcohol
Sepsis
Key investigation is MIDNIGHT CORTISOL which is LOW, compared to true Cushings
What is the medical therapy for Cushing’s disease pre-operatively?
Ketoconazole (mainly)
Metyrapone
Pasireotide - somatostatin
Mifepristone - anti-progestin. But also a good anti glucocorticoid receptor agent.
What are the causes of hyperprolactinaemia?
DRUGS
- phenothiazines (chlorpromazine, prochlorperazine - typical antipsychotics, Dopamine-2 D-2 receptor antagonists that decrease the effect of DA)
- newer antipsychotics (olanzapine, risperidone)
- METOCLOPRAMIDE
other- postpartum, CRF, seizure
Endocrine causes
- PRLoma
- macroadenoma with stalk disruption
- any stalk trauma
- false elevation/ lab error as PRL aggregates in plasma (macroPRLaemia)
What is Sheehan’s syndrome?
Haemorrhagic infarction of the pituitary at the time of delivery, usually associated with a major obstetric complication. Pituitary in pregnancy is twice the normal size and very vascular hence more vulnerable to injury.
Results in:
Hormone deficiencies / partial hypopituitarism.
Failure of lactation.
Failure of return to menses.
How does Diabetes Insipidus present?
What are the types of DI?
What tests would you order to make a diagnosis?
Polyuria
Polydipsia
Risk factors such as pituitary surgery, stalk lesions, craniopharyngioma
Tests:
URINE OSMOLALITY = LOW (Urine is DILUTE!!)
Serum Osmolality normal or elevated
EUC - Na and Ca elevated (or normal). K low normal.
24 hr urine collection - LARGE volume >3L/day.
WATER DEPRIVATION TEST - Urine Osmolality LOW «_space;serum Osm following dehydration
DESMOPRESSIN (= VASOPRESSIN/DDAVP) STIMULATION TEST
- -> CENTRAL DI: > 50% increase in urine osmolality following Desmopressin
- -> NEOHROGENIC DI: No or little < 50% increase in urine Osmolality following Desmopressin
TREATMENT is fluid replacement. If severe and permanent: desmopressin nasal spray or tablets
What are the biochemical features of Addisons?
Hyponatraemia
Hyperkalaemia
Hypercalcaemia
Low BSL
Low AM cortisol
High ACTH
What is the diagnostic approach to a person with HTN and Hypokalaemia?
Test for Hyperaldosteronism:
Aldosterone- renin ratio
–> if renin is suppressed OR if high Aldo/Renin ratio,
Then
SALINE SUPPRESSION TEST (2L NS over 4 hrs)
Normally this should suppress Aldosterone to < 140 nmol /L.
+/- FLUDROCORTISONE SUPPRESSION TEST over several days. On day 4, plasma aldosterone should normally be suppressed to < 170 nmol/L
Then
IMAGING to test lateralisation!
Adrenal CT and ADRENAL VEIN SAMPLING
–> if lateralisation, then adrenalectomy
–> if no lateralisation, then medical management with Spironolactone, Amiloride
What are the DDx for HTN a and hypokalaemia (mineralocorticoid hypertension)?
- Primary Hyperaldosteronism (Conns, adrenal cancer, idiopathic hyperplasia)
- Hypertensive Congenital Adrenal Hyperplasia
- Glucocorticoid resistance
- 11-beta hydroxysteroid dehydrogenase deficiency
- this enzyme catalyses cortisol –> cortisone in mineralocorticoid target tissues, but a deficiency allows cortisol rather than aldosterone to bind to receptor hence causing apparent mineralocorticoid excess.
- auto recessive
= licorice effect - Liddles Syndrome
- auto dominant, defect in mineralocorticoid-dependent collecting tubule Na channel –> increased Na reabsorption
- early onset HTN and Hypokalaemic metabolic acidosis
- LOW RENIN and suppressed/LOW ALDOSTERONE
- ***Note Liddles is TRIAMTERENE not Spironolactone responsive
Which of the following drugs are most likely to interfere with the interpretation of an Aldosterone:Renin result?
- Beta blocker
- ACEI
- ARB
- Spironolactone
- CCB
Answer is Spironolactone, as it is an aldosterone antagonist.
- Beta blocker - causes FALSE POSITIVES as it reduces Renin (all others cause false negatives)
- ACEI - causes false negative
- ARB - causes false negative
- Spironolactone
- CCB - little effect, can leave a patient on this drug during testing
What is the management for Phaeochromocytoma?
Catecholamine producing tumour
Plasma/Urinary metanephrines and catecholamines
(Plasma MN lacks specificity)
CT = MRI, should capture 95% of phaeo’s
MRI better for extra-adrenal tumours
MIBG (Nuc Med scan) most specific but limited sensitivity
DRUGS - (“This blood pressure is a Personal Best “PB”..PROPS to you!”)
Alpha blockade - PhenoxyBenzamine
Beta blockade - Propranolol
Crisis control - Phentolamine, Nitroprusside
SURGERY
What are the hereditary syndromes associated with Phaeochromocytoma?
What gene mutations are associated with Phaeo and Paragangliomas?
MEN 2a and 2b - 50% risk of Phaeo!!! RET ONCOGENE mutation
(Medullary thyroid ca, hyperparathyroidism)
Familial paraganglioma syndrome - carotid body tumour. 20% risk of Phaeo. SDHB (succinate dehydrogenase) GENE MUTATIONS.
(***SDHB most important genetic test!)
VHL (retinal angiomas, CNS haemangioblastoma, renal cell ca, pancreatic/renal cysts) 10-20% risk of Phaeo. VHL mutation
NF type 1 (cafe au laid, neurofibromas), 1% risk. NF1 gene mutation
Premature Menopause.
What are the common causes of premature menopause?
How do you diagnose premature menopause?
Causes:
58% are Autoimmune or idiopathic. Associated with autoimmune thyroid disease, T1DM, Addisons
Turner syndrome 23%
Chemotherapy 7% - cyclophosphamide (BrCa, Lupus patients)
Familial 4%
Other- pelvic surgery or irradiation, gonadal dysgenesis, galactosae is
Diagnosis: 12 months cessation of menses - symptoms of menopause FSH elevated > 20 IU/L is diagnostic Low Oestradiol, elevated gonadotrophins TSH
What is the difference in outcomes between postmenopausal women treated with Oestrogen-Progesterone (combined) HRT VS Oestrogen-only HRT?
Compared to controls, both have increased risk of stroke, DVT, PE.
VTE and BREAST CANCER risk is WORSE WITH COMBINED Oestrogen and Progesterone.
(Hence hormone-dependent Breast cancer is a contraindication to HRT, and VTE a is a relative contraindication)
Oestrogen and Progesterone
- MORE CORONARY HEART DISEASE
- VTEs and BREAST CANCERS
- FEWER Colorectal ca!!
- Fewer fractures (all types, hip etc)
Unopposed Oestrogen: - *** only for women who have had a hysterectomy!!! *** - RISK OF ENDOMETRIAL CANCER with unopposed oestrogen (hence women with an intact uterus need progesterone as well) - MORE STROKE But - fewer CHD - fewer breast cancers - fewer fractures (all types, hip etc)
Unopposed Oestrogen therapy in women without a uterus has a more favourable harm vs benefit profile.
What tests do you order for investigating amenorrhea?
What are the DDx for amenorrhea?
Beta HCG FSH, LH, Oestrogen, PRL Androgen profile = Testosterone, SHBG, FAI, DHEAS TSH pelvic US Pituitary MRI
If oestrogen deficiency - BMD a
Karyotype go if suspect XO
DDx - think anatomically!
Hypothalamic amenorrhea (anorexia, stress)
Pituitary - PRL, Sheehan’s
Thyroid - hyper/hypo
Adrenals - CAH, Hyper/hypo (Cushings/Addisons)
Ovarian - PCOS, Premature menopause incl Turners
Uterine - Ashermans Syndrome (rare, uterine adhesions)
What is the mechanism of PCOS?
What hormonal findings do you expect?
What is the Mx for PCOS?
Increased Androgen production via 2 mechanisms:
- Driven mainly by LH and Insulin (ovarian thecal cells are under LH stimulation)
- Insulin resistance and Obesity RESULTS IN LOWER SHBG –> higher levels of free/active Testosterone (as Testosterone circulates bound to SHBG. SHBG inactivated the androgens)
Hence the OCP is a good treatment as it tackles both mechanisms.
OCP has contraceptive effect (reduces LH) and also causes an INCREASE in SHBG.
PCOS: High testosterone High oestrogen (from aromatisation --> hence increased risk ENDOMETRIAL CANCER) High LH and FSH (LH >>FSH by 3:1) Low SHBG
Ultrasound:
>12 follicles in ovary, measuring 2-9mm diameter
Increased ovarian volume >10ml
Treatment
1. Low dose OCP (oestrogen –> lowers LH & increases SHBG). Major effect is the LH/testosterone suppression.
OCP also confers endometrial protection with cycle regulation/shedding of endometrium with cyclical progesterone
- Androgen blockade with Spironolactone or CYPROTERONE (block androgen receptors so testosterone can not exert its effect, a competitive antagonist of the androgen receptor)
- EFLORNITHINE (topical) - blocks ornithine decarboxylase. Treats hirsutism.
- For fertility- Metformin, Clomiphene (blocks negative feedback of oestrogen in the hypothalamus on LH/FSH release –> net result is increased LH/FSH. Given early/day3 in menstrual cycle)
Features of diabetic amyotrophic
Painful asymmetric proximal motor neuropathy of the lower limbs (may be bilateral)
Initially presents with thigh pain/ tender Prox muscles, progressing to muscle wasting, Loss of knee reflexes
Caused by occlusion of the vasa nervorum of the Prox lumbar plexus and/or femoral nerve.
Associated with poor DM control.
REVERSIBLE — often resolves with time and improves with good glycemic control
MCQ. Which factor inhibits release of Growth Hormone? A. Fasting B. Ghrelin C. Hypoglycaemia D. Somatostatin E. Stress
Answer is Somatostatin.
Roles of somatostatin:
- inhibits GH release
- inhibits secretion of insulin and glucagons
GH is INHIBITED by: Somatostatin hyperglycaemia (hence the glucose load test in Acromegaly) Cortisol Beta-adrenergic activity Obesity FFA Hypothyroidism IGF1 (negative feedback)
GH release is INCREASED by: Deep sleep Fasting Alpha adrenergic activity Stress, hypoglycaemia, exercise AA Thyroxine Ghrelin
What is the action of DPP4 inhibitors and why don’t they cause hypoglycaemic episodes?
DPP4 inhibitors
- reduce the natural degradation of incretins, leading to increased GLP1
- results in suppression of glucagon, but if BSL is too low then glucagon is not suppressed (“glucose dependent glucagon suppression”) — hence these drugs do not cause hypoglycaemia
- glucose-dependent insulin stimulation
- reduced GI motility
- weight neutral
When do you use SPECT CT of thyroid?
Use a SPECT/CT of thyroid to investigate sub-centimetre nodules
Name the 2 most common sites of thyroid cancer spread?
Lung
Bone
HRT in postmenopausal women increases which of the following?
- LDL
- Cardiovascular morbidity
- HDL
- Triglycerides
HRT INCREASES TRIGLYCERIDES!!
Also increases CV morbidity (showed in RCTs)
May increase HDLs
What are the physiological changes in the Endocrine system in the elderly?
HIGH PTH –> bone resorption, osteoporosis
High FSH/LH
High ADH –> HypoNatraemia
Autoimmune THYROIDITIS
LOW GH
LOWE RENIN and ALDOSTERONE –> increased risk of HyperKalaemia
What is the definition of Osteopaenia?
How do you manage Osteopaenia?
T score lower than -1.0.
Management is to modify osteoporosis risk factors.
- Diet and weight-bearing exercise, BMI, adequate Ca and Vit D
- Only consider oral Calcium supplement if dietary intake is insufficient (need 1000mg/d = 3 servings)
- Oestrogen/Progesterone in ALL women with POF.
- In steroid-induced Osteopaenia, can start bisphosphonates at T score lower than -1.0 OR if they have received 5mg Pred for at least 3 months
Common causes of Hypocalcaemia
CRF
HypOparathyroidism
Vit D def
** HYPOMAGNESAEMIA
