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.
acromegaly
IGF-1 has a long half-life of 18 to 20 hours - screening test
Measurement of GH during OGTT (with 75 g glucose load) is the standard method –> confirm the diagnosis of acromegaly
Treatment of acromegaly:
– Surgery is first line
– Followed by octreotide (somatostatin analogue) aiming to normalise IGF-1.
– Add cabergoline to patients not fully controlled on octreotide.
– Pegvisomant- Growth hormone receptor antagonist.highly effective in acromegaly.
Cure defined as growth hormone suppression to <1ng/ml after 75g glucose.
cinacalcet
Allosteric activation by binding to the calcium-sensing receptor
In summary, Cinacalcet is a calcimimetic agent that:
– mimics the action of extracellular calcium
– binds to the calcium sensing receptor
– reduces PTH secretion
– Increases sensitivity of CaSR to extracellular calcium.
– moves the CaSR-PTH concentration response curve to the left therefore lowering the setpoint.
Indications:
◦Primary hyperparathyroidism in whom:
– Fail or have contraindications to surgery
– Do not wish to have surgery
– Do not meet the current guidelines for surgery
◦Secondary hyperparathyroidism
◦Parathyroid carcinoma
2013 guidelines for parathyroid surgery in asymptomatic primary hyperparathyroidism
◦Serum calcium of >0.25mmol/L
◦Creatinine clearance <60mls/min
◦24-h urine for calcium >400 mg/d (>10mmol/d) and increased stone risk by biochemical stone risk analysis
◦Presence of nephrolithiasis or nephrocalcinosis by x-ray, ultrasound, or CT score
◦Age <50
Evidence in support of surgery:- sustained improvement in bone density
– reduction in fractures
– reduced frequency of kidney stones
– improvement in some neuro cognitive elements
In asymptomatic PHPT who do not undergo parathyroid surgery, check serum calcium and creatinine annually.
FGF-23
Action is dependent on parathyroid hormone
High Phosphate = High FGF-23
Low Phosphate = Low FGF-23
Increased FGF-23 in hypophosphatemic disease:
◦Autosomal dominant hypophosphataemic rickets
◦X-linked hypophosphataemic rickets
◦Oncogenic osteomalacia.
CUSHINGS SYNDROME
Yes if at least 2 of these tests are abnormal:
1) 24 hour urinary free cortisol.
2) Late night salivary cortisol.
3) Low dose(1mg) dexamethasone suppression test.
4) Late evening serum cortisol.
If ACTH is inappropriately normal or High, think of ACTH dependent causes:
– Cushing’s disease(Pituitary adenoma)
– Ectopic ACTH syndrome
– Ectopic CRH syndrome
If ACTH is undetectable or low, think of ACTH independent causes:
– Adrenal adenoma
– Adrenal carcinoma
– Micro/macronodular hyperplasia.
Graves disease clues
TSH receptor antibodies present.
Exophthalmos,pretibial myxoedema,acropachy, which do not occur with other causes of hyperthyroidism.
large goitre and bruit present.
high thyroid uptake of radioactive iodine
Increased flow on colour-flow Doppler.
Decreased radio iodine uptake
1) thyrotoxicosis factitia (patients on thyroxine therapy)
2) subacute thyroiditis
3) painless thyroiditis
4) silent thyroiditis
5) postpartum thyroiditis
6) ectopic thyroid tissue
silent thyroiditis clues
– Absent or low uptake on radioiodine scan (uptake of <1%), in contrast to generally normal uptake in toxic MNG.
– Often there is evidence of thyroid autoimmunity (i.e., positive thyroid peroxidase antibodies)
toxic multi nodular goitre clues
– Onset of symptoms is more insidious and symptoms less dramatic than for Graves’ disease.
– Stigmata of Graves’ disease, including exophthalmos and pretibial myxoedema, are ABSENT.
– In toxic MNG, thyroid scan shows multiple hot and cold areas consistent with areas of autonomy and suppression
– Thyroid ultrasound is not helpful
– Treatment is with iodine 131 or PTU/carbimazole.
woman with type 1 (insulin-dependent) diabetes mellitus is at most risk of developing
hashimotos thyroiditis
Hashimoto’s thyroiditis (chronic lymphocytic thyroiditis) Clues
– usually asymptomatic but some patients may complain of a feeling of tightness or fullness in the neck.
– no neck pain
– firm, irregular, nontender goiter
– Auto-immune-mediated inflammation of the thyroid gland with release of thyroid hormone resulting in transient hyperthyroidism, frequently followed by a hypothyroid phase before recovery of normal thyroid function
– diagnosis is best confirmed by radioiodine uptake of <1% during the hyperthyroid phase of the illness.
– high titers of circulating antibodies to thyroid peroxidase and thyroglobulin.
– Radioactive iodine uptake (RAIU) is variable
Drug induced prolactinaemia
Dopamine acts on the pituitary as an inhibitor of prolactin secretion.
Blockade of dopamine D2 receptors –> can cause hyperprolactinaemia in males and females.
- Antipsychotics:
phenothiazines
haloperidol
risperidone - Antiemetics:
metoclopramide
domperidone - Antidepressants:
Tricyclics
MAOIs - Opiates
- Antihypertensives:
Verapamil
Methyldopa
Propylthiouracil in pregnancy risk
hepatotoxicity
testosterone level
active testosterone = free testosterone
inversely corr. with SHBG levels Conditions that decreases SHBG concentrations (high lvl of free testosterone): 1) Moderate obesity 2) Nephrotic syndrome 3) Hypothyroidism 4) Use of glucocorticoid, progestins and androgenic steroids. 5) Diabetes 6) PCOS
Condition that increases SHBG concentrations:
1) Aging
2) Hepatic cirrhosis
3) Hyperthyroidism
4) Use of estrogens
5) HIV
6) Anorexia
7) Pregnancy
acromegaly assoc ca
bowel ca
anti-thyroid s/effect
Carbimazole= Cholestatic picture
PTU = HePatocellular damage picture
most common monogenetic cause of obesity
MC4-R mutation
leptin
peptide hormone synthesized in adipocytes in proportion to cell size.
Functions:
1) Inhibits food intake by reducing the expression of neurotransmitters that increase food intake ie: Neuropeptide Y and agouti-related peptide.
2) Increases energy expenditure.
Ghrelin
– Ghrelin is a peptide hormone secreted from the stomach.
– It increases preprandially and stimulates appetite.
– Higher levels found in leaner subjects.
– Elevated in Prader willi syndrome
– Reduced in post gastric bypass surgery
Hormones that inhibits food intake
Gut:
1) Peptide YY
2) Oxyntomodulin
3) Pancreatic polypeptide
4) Cholecystokinin
5) Glucagon-like peptide 1
Adipose tissue:
1) Insulin
2) Leptin
Hypothalamus:
1) Cocaine and Amphetamine regulated transcript (CART)
2) Alpha melanocyte stimulating hormone (αMSH)
Hormone that stimulate appetite:
Gut:
1) Ghrelin.
Hypothalamus:
1) Neuropeptide Y
2) Agouty-related peptide (AgRP)
MEMORY TIP: Easier to remember the hormones that stimulate appetite (Only 3)- Ghrelin, AgRP, NPY.
The rest inhibits appetite.
Diabetic meds that dont cause hypoglycemia.
Mnemonic MATES.(Metformin, Acarbose, Thiazolidinediones, Exenatide, Sitagliptin)
“MATES don’t give you hypos!!”
SIADH
– A low plasma osmolality
– An inappropriately elevated urine osmolality (above 100 mosmol/kg)
– A urine sodium concentration usually above 40 meq/L
– Low BUN and serum uric acid concentration
– A relatively normal plasma creatinine concentration
– Normal acid-base and potassium balance
– Normal adrenal and thyroid function
Pseudohyperkalemia
Causes of pseudohyperkalemia:
1) Hemolysed sample
2) Hereditary spherocytosis
3) Familial pseudohyperkalemia
4) Marked leukocytosis or thrombocytosis
Suspect this when there is no apparent cause for elevation in asymptomatic patient.
most common cause of ambiguous genitalia
CAH
– 90% is due to 21-Hydroxylase deficiency.
– most common cause of ambiguous genitalia.
– Features: ambiguous genitalia, precocious puberty, salt losing adrenal crisis, hyperpigmentation.
– Treat with hydrocortisone, fludrocortisone.
adrenal gland area - secretions
Zona glomerulosa- aldosterone
Zona fasciculata- cortisol
Zona reticularis- DHEA, Androstenedione
Medulla- Adrenaline, NorAdrenaline, dopamine
Steroid Induced Osteoporosis
Mechanisms of Steroid Induced Osteoporosis include:
- Direct inhibition of osteoblast function
- Direct enhancement of bone resorption
- Inhibition of gastrointestinal calcium absorption
- Increased urine calcium loss
- Inhibition of sex steroids
Hyperglycaemia caused by steroid
Glucocorticoid causes hyperglycemia by:
1) Stimulation of gluconeogenesis
2) Increase glucose production from protein
3) Increased pancreatic insulin production (Corticosteroids counteract the effect of insulin)-so pancreas have to produce more insulin!!
Hypogonadotrophic hypogonadism
primary cause
Primary: the defect lies at the level of the testes (low testosterone and elevated gonadotropins):
– Klinefelter’s syndrome 47,XXY
– Noonan’s syndrome: phenotypic and genotypic males with physical signs of classic female Turner syndrome.
– Y-chromosome micro-deletion: usually spermatogenesis affected. Testosterone levels normal.
– Cryptorchidism (undescended testes).
– Infections: orchitis related to mumps is the most common infection. Spermatogenesis is more affected than androgen production.
– Drugs: alkylating agents, such as cyclophosphamide and chlorambucil, are the most notable examples. The seminiferous tubules are usually the main site of damage, although testosterone production can also be affected.
– Ketoconazole also decreases testosterone production.
– Testicular trauma, torsion, or irradiation.
– Varicocele: causes increased temperature and/or accumulation of tissue metabolites in the testes.
– Myotonic dystrophy
– Auto-immune orchitis: a rare cause of primary hypogonadism.
– Radiation exposure.
– Environmental toxins (e.g., heavy metals, chemical, pesticides).
– Excessive alcohol consumption.
– Human immunodeficiency virus (HIV).
Hypogonadotrophic hypogonadism
secondary cause
Secondary hypogonadism, the defect lies at the level of the hypothalamic-pituitary axis and is associated with low testosterone and low (or inappropriately normal) gonadotropins:
– Combined pituitary hormone deficiency (CPHD): progressive stepwise onset of pituitary dysfunction during childhood or even adult life.
– Isolated hypogonadotropic hypogonadism (IHH): caused by a complete or partial failure of GnRH secretion from the hypothalamus, leading to a reduction in FSH and LH release. Many genetic mutations may result in IHH ie: Kallmann’s syndrome
– Hyperprolactinaemia: elevated prolactin level (from any cause) suppresses GnRH.
– Pituitary tumours and pituitary apoplexy: causes compression of gonadotrophs (basophilic cells of the anterior pituitary specialised to secrete FSH or LH).
– Parasellar tumours: e.g., meningioma, craniopharyngioma, Rathke’s cleft cyst, metastases.
– Drugs: opioids, high-dose glucocorticoids, GnRH analogues, exogenous oestrogens or androgens.
– Infiltrative diseases (e.g., haemochromatosis, sarcoidosis, histiocytosis): destruction of the gonadotrophs is considered to be the mechanism of action.
– Irradiation
– Severe systemic illness: this can suppress the hypothalamic-pituitary-gonadal axis; when the illness resolves, the axis usually recovers.
– Head injury: trauma, surgery.
– Chronic disease: common examples include diabetes/insulin resistance, coronary artery disease and HTN, uraemia, sickle cell disease, thalassaemia, obesity, COPD, HIV, or liver cirrhosis.
– Glucocorticoids: Cushing’s syndrome or exogenous glucocorticoid use cause suppression of GnRH synthesis.
thyroid nodule
suspicion of malignancy;
Positive family history of medullary ca or MEN
Rapid tumour growth
Firm or hard nodule
Fixation of nodule to adjacent structure
Paralysis of vocal cords
Distant mets
PET incidentaloma-carries a high risk of malignancy
USS features of malignant thyroid nodule
solid markedly hypoechogenecity intranodular vascularity absence of halo irregular margin central microcalcification cervical LN >4cm Single cold nodule on radionuclide scan
Microcalcification + irregular margin 95% specific for thyroid cancer.
Microcalcification + hypoechoic 96% specific for thyroid cancer.
mx of thyroid nodule
Thyroid nodule more than 4cm with benign cytology has very high false negative rate and should be managed with diagnostic lobectomy to exclude thyroid malignancy regardless of FNA result.
Total thyroidectomy if primary tumour is >1cm or if extranodal extension or metastases present
highest rate of positivity to anti-thyroid peroxidase antibody
autoimmune thyroiditis.
anti-TPO antibody is positive in 90-100%.
Thyroid cancer
Types:
1) Thyroid epithelium (papillary, follicular, anaplastic)
2) Calcitonin producing C cells (medullary)
Tumor marker:
1) Thyroglobulin for Thyroid epithelium (papillary, follicular, anaplastic) .
2) Calcitonin for Calcitonin producing C cells (medullary) .
thyroid cancer Rx
1) Papillary and follicular cancer:
– Surgery either total or near total thyroidectomy (Total If tumor >1cm) +/- LN dissection
– For papillary cancer < 1cm (microcarcinoma), no ablation required but TSH suppression still necessary.
– Radioactive iodine (RAI) ablation of residual thyroid tissue post-operatively.
– After ablation of normal thyroid in this way, RAI may be used to localize residual disease (tumor surveillance)
– To minimize risk of recurrence, patient is given suppressive doses of levothyroxine (sufficient to suppress TSH levels below the normal range)-LIFELONG therapy.
– Monitor patient’s progress with serum thyroglobulin levels (measurement of thyroglobulin is most sensitive when TSH is high but this requires the withdrawal of levothyroxine therapy)
– So give Recombinant human TSH to stimulate thyroglobulin without stopping thyroxine therapy.
– If thyroglobulin is detected, this suggests recurrence, so proceed with whole body 131-I scan.
2) Anaplastic carcinomas and lymphoma:
– These do not respond to radioactive iodine, and external radiotherapy produces only a brief respite.
– Poor prognosis.
3) Medullary cancer:
– Total thyroidectomy and wide lymph node clearance
– Tumour responds poorly to treatment.
– RET oncogene sequencing and contact family for screening.
– Follow up disease with serum calcitonin.
– Consider MEN II.
– prophylactic thyroidectomy before age 20 for carriers of RET mutation.
Principle of investigations of a thyroid nodule
1) Start with a good history and examination.
2) Check serum TSH to see if nodule is hyperfunctioning or not.
3) If TSH low, proceed with thyroid technetium scan.
If hyperfunctioning, evaluate and treat for hyperthyroidism.
If not hyperfunctioning, proceed with diagnostic USS.
4) But if TSH is normal or high, proceed with diagnostic USS.
5) If nodule is identified on USS, proceed with FNA.
6) If biopsy is non diagnostic, repeat FNA.
So basically series of investigation can be summarized as follow: “TSH, +/- technetium scan, USS and FNA.”
periodic paralysis associated with Grave’s disease
– due to transient severe hypokalaemia often following high carbo meal and severe exercise.
– usually seen in Asian subjects.
– ONLY occurs during thyrotoxic phase of illness.
Reasons to consider Tc99 scan and radioiodine treatment is patients with subclinical hyperthyroidism
1) Atrial fibrillation
2) Osteoporosis
3) TSH <0.1
TSH 0.1- 0.4 warrants observation
growth hormone deficiency Clues
– History of pituitary disease
– Symptom of lethargy and weight gain (reduced lean mass, increased fat mass)
Gold standard is insulin tolerance test.
– Stimulated GH of <3microgram/L indicate severe GH deficiency.
Treatment is with GH injections (not funded)
Concept: Hypoglycemia STIMULATES Growth Hormone release.
hyperprolactinaemia approach
1) In females- ALWAYS rule out pregnancy first
2) Exclude hypothyroidism by checking TSH (TRH stimulates prolactin release)
3) Is the patient on certain drugs that can cause high prolactin?
– Antipsychotics: haloperidol, risperidone
– Antiemetics: maxalon, domperidone
– Antidepressants: Tricyclics, MAOIs.
– Anti-HT: Verapamil, methyldopa
4) If all above negative, perform MRI pituitary.
Non functioning pituitary adenoma vs prolactinoma.
Non-functioning adenomas:
– usually presents with mass effect (bitemporal hemianopia)
– hypopituitarism
– incidentaloma
– very high prolactin (up to 10 fold) due to stalk pressure
Treatment of non-functioning pituitary adenoma.
– surgery (trans-sphenoidal adenomectomy)
– radiotherapy reduces risk of tumour recurrence.
– complication: hypopituitarism at 10 years.
Prolactinoma:
– commonest secretory pituitary adenoma.
Macroadenoma >10mm with prolactin >5000 mIU/L.
Treatment of prolactinoma:
– Treatment indications for prolactinoma: Hypogonadism, Galactorrhea, Macroadenoma.
– Cabergoline is the drug of choice.
– Tumor shrinkage in 80% of macroadenomas
– Side effect is valvular regurgitation at high doses.
cushings synd most specific SIGN
skin changes - easy bruising/poor healing
-absent in pseudo-cushings
Cushing’s disease - most specific for diagnosis
-cortisol suppression after high dose (8mg/day) dexamethasone suppression test.
Failure to suppress cortisol after 2 mg/day(low dose), with suppression on 8 mg/day(high dose), indicates Cushing’s disease.
Failure to suppress cortisol on 8 mg/day indicates adrenal neoplasm or ectopic ACTH syndrome.
Prolactinoma in pregnancy
For MICROadenoma (<10mm):
1) Stop cabergoline once pregnancy test positive.
2) Monitor visual fields during pregnancy.
3) Postpartum MRI after 6 weeks.
For MACROadenoma (>10mm):
1) Consider surgery before getting pregnant.
2) Monitor visual fields.
3) Commence bromocriptine if vision compromised.
4) Consider high dose steroid or surgery if vision threatened or adenoma hemorrhage.
5) Postpartum MRI at 6 weeks.
secondary causes of hyperlipidaemia
Cholesterol:
- Hypothyroidism
- Cholestatic liver disease
- Nephrotic syndrome
- Pregnancy
- Cyclosporin
Triglycerides
- Alcohol
- Oral estrogen, tamoxifen, aromatase inhibitors
- Diabetes
- Renal disease
- Other drugs: Thiazide, B- blockers, steroids, Interferons, sirolimus, asparaginase,isotretinoin, clozapine,olanzapine, protease inhibitors.
HDL lowering:
-Anabolic steroids, smoking.
carbimazole MOA
-interfere w/ thyroid peroxidase activity.
Carbimazole inhibits thyroid hormone synthesis by interfering with thyroid peroxidase-mediated iodination of tyrosine residues in thyroglobulin
MODY 2
Glucokinase (ch 7) decreased insulin secretion no micro/macrovasc cx no treatment required, EXCEPT in pregnancy -incidental finding, no fam hx
MODY 3
HBF-1a (Ch 12)
progressive b-cell failure
increased OGTT/HDL
sensitive to sulphonylurea
