endo Flashcards
MEN-1
triple Ps
Parathyroid adenomas
Pancreatic tumors
Pituitary adenomas
MEN 2A
medullary thyroid carcinoma
Parathyroid hyperplasia
pheo
MEN 2b
mucosal neuroma
marfanoid body habitus
medullary thyroid carcinoma
pheo
Graves Disease clin fx
peak age: 40-60 yrs pretibial myxoedema exophthalmos (risk factors: smoking, high TSI, trauma) goitre vitiligo dermopathy acropathy/onycholysis
relapse:
- usually in 3-6 mths
predictors: large goitre/ +ve tsab at time of stopping therapy
Graves dis, dx test
TPO (90%)
Thyroid stimulating immunoglobulin (TSI)
thyroid scintiscan - diffuse
antithyroid therapy
- antithyroid drugs (thionamide)
-carbimazole –> methimazole –> inhibit organisation & coupling (rarely cause cholestatic hepatitis)
-PTU –> blocks peripheral conversion of T4 to T3
(rarely cause hepatitis & aplastic anaemia)
cx: allergy, agranulocytosis - radioactive iodine
cx - hypothyroid, teratogenesis - surgery (thyroidectomy)
indication for graves - large ops goitre/severe opthalmopathy/failure of remission with drugs
Gestational hyperthyroidism
-bHCG acts as TSH in early pregnancy
-in 1st trimester (9-12/40)
-usually resolve by 20/40 -if persist need RX (think graves)
-TSi & anti-thyroid drug cross placenta
aim of rx - mom low normal TSH, high normal T4/ fetes euthyroid
-1st trimester - PTU/ carbimazole after
-surgery
Radioactive iodine contraindicated
need to monitor fetus - mom on anti-thyroid meds, +ve TSI
Cx:
perinatal/maternal mortality
pre-eclampsia
neonate thyrotoxicosis/hypothyroid
TSH decreases during the first trimester but increases during the 2nd and third trimester. (Inverse relationship with HCG)
post-partum thyroiditis
6/40 to 3 mths postpartum
thyrotoxic phase then hypothyroid
rx seldom required
empaglifozin
Empagliflozin is an inhibitor of the sodium glucose co-transporter-2 (SGLT-2) - in the proximal tubules -Blocking SGLT-2 reduces blood glucose by blocking glucose reabsorption in the kidney --> excreting glucose via the urine. -increased risk of ketoacidosis/UTI EMPA-REG trial - empag reduce CVS risk Other effect of empag: – Reduction in HbA1c or 0.5‐0.75% – Mild weight loss – Mild reduction in blood pressure – Reduced uric acid – Reduced microalbuminuria
cushings syndrome
Only 3 biochemical tests are needed to work up Cushing’s syndrome:
1. Urinary free cortisol - confirms the clinical diagnosis of Cushing’s syndrome.
- plasma corticotropin - to separate corticotropin dependent from corticotropin independent causes of Cushing’s syndrome. It also helps to separate eutopic from ectopic secretion of corticotropin.
- imaging of the adrenal gland would then be necessary if the plasma corticotropin is unmeasurable. - plasma cortisol - to determine the success or failure of surgery (transphenoidal microadenomectomy or adrenalectomy) ie: If unmeasurable on the morning post surgery, then the surgery was successful.
The dexamethasone suppression test was previously used to separate corticotropin-dependent from corticotropin-independent Cushing’s syndrome. However, this is now done by measuring the plasma corticotropin level.
The positive predictive value of dexamethasone suppression test is estimated to be only around 0.4% and therefore should no longer be used.
adiponectin
- Adiponectin is produced solely in adipose tissue.
- Levels are inversely related to body fat.(ie: high body fat, low adiponectin)
- It promotes fatty acid catabolism.
- Low adiponectin levels predict future diabetes in Pima Indians.
- Mutations in adiponectin promoter region are associated with insulin resistance.
Increases with:
1) exercise
2) calorie restricted diet- induced weight loss
3) weight loss following bariatric surgery
4) thiazolidinedione therapy
Decreases with:
1) Obesity (Increase body fat)
2) Diabetes
thyroid hormone
Factors contributing to low T3
- High cortisol levels
- Circulating inhibitors of deiodinase activity: eg. Free fatty acids
- Drugs which inhibit deiodinase, propranolol, amiodarone
- Cytokines
Factors contributing to low T4
- Reduced hormone binding proteins
- Reduced binding to binding proteins
Factors contributing to low TSH
- Dopamine
- Glucocorticoids
vit D synthesis
- 7-dehydrocholesterol to cholecalciferol (UV light on skin)
- Cholecalciferol to calcidiol in liver
- Calcidiol to calcitriol in kidneys.
testosterone/estradiol binds to SHBG/albumin
decreases SHBG concentrations:
1) Moderate obesity
2) Nephrotic syndrome
3) Hypothyroidism
4) Use of glucocorticoid, progestins and androgenic steroids.
5) Diabetes
increases SHBG concentrations:
1) Aging
2) Hepatic cirrhosis
3) Hyperthyroidism
4) Use of estrogens
5) HIV
6) Anorexia
7) Pregnancy
hypercalcemia effect on kidney
PCT – inhibits phosphaturic action of PTH
LOH – Inhibits salt reabsorption
Distal tubule – Inhibits PTH mediated calcium reabsorption
Collecting tubule- Inhibits ADH action.
anion gap
calc = [ Na + K] - [Cl + HCO3]
normal anion gap = 4-12
NAGMA CAGE •Chloride excess •Acetazolamide/Addisons •GI causes – diarrhea/vomiting, fistulae (pancreatic, ureters, billary, small bowel, ileostomy) •Extra – RTA
ABCD •Addisons (adrenal insufficiency) •Bicarbonate loss (GI or Renal) •Chloride excess •Diuretics (Acetazolamide)
HAGMA LTKR lactate toxin ketones renal or CATMUDPILES •CO, CN •Alcoholic ketoacidosis and starvation ketoacidosis •Toluene •Metformin, Methanol •Uremia •DKA •Pyroglutamic acidosis, paracetamol, phenformin, propylene glycol, paraladehyde •Iron, Isoniazid •Lactic acidosis •Ethylene glycol •Salicylates
PCOS
can be diagnosed with hirsutism and oligomenorrhea.
-serum testosterone concentrations may be in the normal range 0.69 to 2.1 nmol/L OR elevated but below 5.2 nmol/L.
High-resolution pelvic ultrasonography with a transvaginal probe can identify ovarian follicles and cysts as small as 3 to 5 mm in diameter. It is therefore a safe and effective way to look for polycystic ovary morphology and to screen for ovarian androgen-secreting tumors.
Liraglutide
GLP-1 analogue -lower glucose -slight reduction in weight and BP -assoc with increased HR LEADER trial 2010 - The study showed that the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo.
HBA1C calculation
Calculation of estimated average glucose: Estimated Glu (mmol/l) = 1.59 x HbA1C − 2.59
papillary thyroid cancer
Serum thyroglobulin (TG) is considered an excellent marker of thyroid recurrence. After recombinant TSH stimulation, a value less than 2 ng/mL has a high negative predictive value. However, the principal limitation of serum TG measurement is the interference by anti-TG antibodies (anti-TGAb).
A temporary rise in anti-TGAb level may occur during the first 6 months after radioiodine therapy, which might be a sign of the effectiveness of treatment, since anti-TGAb values return to original value or below after 6 months.
In the absence of disease, anti-TGAb will progressively decrease and disappear within the first 2 years of follow-up.
papillary and follicular thyroid ca monitor -
thyroglobulin
medullary thyroid cancer monitor -
calcitonin
mx of hypoglycaemia post-exercise
• reduce the long‐acting insulin dose overnight after the exercise undertaken that day; for example, the dose of long‐acting insulin could be reduced from 10–20% (Taplin et al 2010), and in some cases up to 50% (Toni et al 2006)
• basal insulin rates overnight in CSII may need to be reduced by 20‐30%.
• ensure blood glucose is above 7 mmol/L before going to bed (Whincup and Milner 1987; Tansey et al 2006)
• always consume at least 10–15 g carbohydrate before bed after a day of exercise
(Whincup and Milner 1987), preferably as a low‐GI food or with a mixed meal, such as a glass of milk, to aid a slow but persisting rate of glucose absorption into the blood stream.
• in higher risk settings after days of unusually intense or long‐duration physical activity, consider setting the bedroom alarm clock in the early morning hours to check blood glucose at those times, and to supplement with carbohydrate as required.
• monitor blood glucose continuously, to help in recognising asymptomatic hypoglycaemia (monitoring can include both retrospective and real‐time systems) (Riddell and Perkins 2009); real‐time monitoring systems often have a hypoglycaemia alarm triggered by a threshold blood glucose level, to help avoid severe hypoglycaemia
de Quervain’s thyroiditis(subacute/granulomatous thyroiditis)
– abrupt onset of viral-like illness, with fever,myalgia, malaise,pharyngitis, and accompanying symptoms of thyrotoxicosis, such as palpitations, tremor, and heat intolerance.
– Thyroid pain and tenderness.
– very low thyroid uptake on nuclear scan
– high erythrocyte sedimentation rate.
– Normal or decreased vascular flow on doppler.
Infectious, suppurative, or acute thyroiditis
– Pharyngeal abscess is usually present, with dysphagia as a prominent symptom.
– Unlike in subacute/granulomatous thyroiditis, there may be skin erythema over the painful thyroid.
– White blood cell count: elevated.
– FNA biopsy: polymorphonuclear neutrophils. Gram stain shows organisms.
Familial Hypocalciuric hypercalcemia
– benign cause of hypercalcemia
– autosomal dominant
– results from an Inactivating mutation in the Calcium sensing receptor(CaSR)
– the inactivating mutation of the CaSR in FHH makes the parathyroid gland less sensitive to calcium.
– This means that a higher than normal serum calcium concentration is required to reduce PTH release
Clinical findings: usually have positive family history usually asymptomatic Hypercalcemia Hypocalciuria (24-hour urinary calcium excretion is typically below 200mg/day) High normal serum magnesium. Normal renal function Normal PTH Normal phosphate Therefore the best test is to do a 24 hour urine for urinary calcium excretion.
Also calculate Ca/Cr clearance ratio:
Ca/Cr clearance ratio = (24 hr Urine Ca x Serum Cr) /(24 hr Urine Cr x Serum Ca)
If <0.01 = FHH
If >0.02 = Primary hyperparathyroidism
Bisphosphonate s/effects
Body as a Whole: hypersensitivity reactions including urticaria and angioedema.
Myalgia, malaise, asthenia and rarely, fever have been reported with FOSAMAX, typically in association with initiation of treatment. Rarely, symptomatic hypocalcaemia has occurred, generally in association with predisposing conditions. Rarely, peripheral oedema.
Gastrointestinal: nausea, vomiting, oesophagitis, oesophageal erosions, oesophageal ulcers, rarely oesophageal stricture or perforation, and oropharyngeal ulceration; rarely gastric or duodenal ulcers.
Localised osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis)
Musculoskeletal: bone, joint, and/or muscle pain,joint swelling; low-energy femoral shaft fracture.
Nervous System: dizziness, vertigo, dysgeusia.
Skin: rash (occasionally with photosensitivity), pruritus, alopecia, rarely severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Special Senses: rarely uveitis, scleritis or episcleritis.
Pregnancy in obesity Cx
◦Gestational hypertension ◦Pre-eclampsia ◦Gestational diabetes ◦Preterm premature rupture of membranes ◦Preterm delivery ◦Fetal Macrosomia (Birthweight >4000g) ◦Placenta previa ◦Placental abruption ◦Operative vaginal delivery
hyponatremia with low plasma osmol
- Hyponatremia secondary to renal failure,
- SIADH (hypotonic hyponatremia), the inappropriately high urinary osmolality and high urinary sodium of >40 mEq/L.
- thiazide induced.
turner syndrome
Karyotype 45XO/46XX
Recombinant human growth hormone therapy should be initiated as soon as the height of a girl with Turner syndrome falls below the fifth percentile for age, which usually occurs between two and five years of age. Growth hormone should initially be given subcutaneously in a typical dose of 0.375 mg/kg per week (0.053 mg/kg per day).
studies demonstrate that early initiation of growth hormone therapy is important to achieve clinically significant increments in height, and that higher doses (eg, above 0.045 mg/kg per day) yield additional benefit
Addison’s disease
Symptoms:
– weakness, fatigue, N+V, abdo pain, postural BP drop.
Signs:
– *Hyperpigmentation(due to high ACTH), Hypotension, dehydration, weight loss,
loss of axillary and pubic hair in females.
Labs:
– Low Na, High Potassium, Metabolic acidosis, Low T4, High TSH.
– Low aldosterone, High renin.
– Screening test with Early morning cortisol 450 rules out(provided pt not on steroid).
– If level between 150-450, do Short synacthen test to CONFIRM diagnosis.
Cortisol of >550 excludes adrenal failure unless recent pituitary damage.
– High ACTH and High renin indicates primary adrenal insufficiency.
* Hyperpigmentation is caused by the stimulant effect of excess adrenocorticotrophic hormone (ACTH) on the melanocytes to produce melanin.
