Endocrinology Flashcards
In a pituitary adenoma, which is the first hormone to fall?
Gonadotrophins (sex hormones), then GH and ACTH. ACTH rarely falls due to an anterior pituitary adenoma.
Prolactin increases!
What is the Mx for a pt with metastatic insulinoma (inoperable) having hypos?
Somatostatin
What is the most common cause of a hot nodule (one are lighting up on technetium thyroid scan?
Activating somatic mutations of the TSH receptor
What is the most common cause of hyperosmolar hypnoatraemia?
Hyperglycaemia
Is the urine dilute or concentrated in DI?
Dilute
Cannot concentrate urine in DI
Urine osmo > 600
Urine osmo
T/F. Hyponatraemia is associated with OP.
True
Vasopressin is an effective Tx for hyponatraemia? T/F
True
Hyponatraemia with urine Cosmo
Primary polydipsia
Low solute intake
Beer protomania
Hyponatraemia with urine osmo >=100. Urine Na
Means low effective arterial blood volume If ECF expanded consider - HF - LF - nephrotic sundrome
If ECF reduced, consider
- Diarrhoea, vomiting
- Third spacing
- remote diuretics
Hyponatraemia with urine osmo >= 100, Urine Na >30 mol/L. DDx?
Diuretics or kidney disease. If no, then consider: If ECF reduced consider: - Vomitng - primary adrenal insufficiency - renal salt wasting - cerebral salt wasting -occult diuretics
If ECF normal, consider
- SIADH (euovolaemic hypotonic hyponatraemia with inappropriately dilute urine and normal renal Na handling)
- secondary adrenal insufficiency
- occult diurectis
What changes do you get with anorexia nervosa in regards to: LH, FSH, oestrodial and testerone GH Cortisol TSH, T3, T4, rT3
Low LH, FSH oestrodial and tester one
High GH, low OGF-1
High cortisol due to hypothalamic-pituitary renal axis activation
Low/normal TSH, low T3, rT3 is high
Paragnagliomas. DDx for sympathetic PGL and parasympathetic ganglioma?
Sympathetic PGL - adrenal: phaeo 70% - Extraadrenal 10% Parasympathetic - Head and Neck PGL. Carotid tumours
What is the management of a pituitary adenoma on MRI?
Basic WU - PRL, IGF-1
Macro, >1 cm 0.2%. Clinical evaluation for hypopit/hypersecretion, mass effect.
Growth over time occurs in 10%
Why is PTU preferred in the 1st trimester of pregnancy?
Carbimazole embryopathy
Why is thionamide (carbimazole) preferred in 2nd trimester?
Hepatic toxicity of carbimazole
How much should you increase thyroxine in pregnancy?
Increase by 30%.
What are the changes in TSH, TBG in pregnancy?
TSH decreased in 1st TM
Oestrogen increase TBG
MOA of Na-glucose cotransporter 2 (SGLT2) inhibition?
Action on promximal tubule. Inhibits glucose absortpion -> glycosuria
Dabagliflozin/canagliflozin
Inhbits HbA1c lowering by 0.5-1.0%
No hypoglycaemia
200-600 ml extra fluid loss so caution with loop diuretic
Risk of genito-urinary infection esp women 8% vs 1%
What are the adverse effects of testosterone replacement?
Erthrocytosis/elevated haematocrit is a CI. Common AE.
Increased CV events in TT
Worsens untreated cases if OSA
Somatostatin analogues. MOA of Somatostatin, Pasireotide, Octreotide/Lantrotide?
Somatostatin act primarily through 1,2,3,4,5 receptor somatostatin subtypes
Pasireotide act primarily through 1,2,3 and 5 receptor somatostatin subtypes
Lantreotide/Octreotide act primarily through 2 SS receptor type
What somatostatin expression is excreted by a GH screwing, cortisol secreting, promactinoma and carcinoid tumour?
carcinoid SST2
GH-secreting - SST2 and SST5
Cortisol secreting SST5
Prolactinoma SST5
What are the risk associated with oestrogen replacement therapy in post menopausal women?
Stroke, VTE
Fracture risk decreased
What are the risk associated with oestrogen replacement therapy in post menopausal women?
CAD Stroke VTE Breast cancer Fracture risk and colorectal cancer risk decreased
Is transdermal or oral route preferred in post menopausal HT?
Transdermal as less AE
What tests are performed for Pheo? which medications interfere with the test?
24 hr fractionated catecholamines/metanephrines (sen and spec)
Plasma fract metanephrines (sen but not specific)
Interference - nicotine, paracetamol, sotalol, methyldopa, TCAs
Chromogranin A is secreted by pheo and elevated in 80% of cases
What are the Ddx in Hypophosphataemia in 24 hour urine low PO4 and high PO4?
Low urine = appropriate = intestinal (decreased intake, EtOH, Vit D def, PO4 binders) or cellular shift (referring syndrome, glucose infusion, salicylate poison, hyperventillation, catecholamines, resp alkalosis)
High urine = inappropriate = renal wasting -> HPTH or tubular defect e.g. FGF23 medicated Tumour induced osteomalacia if 1,25D low
What are the most specific signs of Cushing’s syndrome?
Skin atrophy
Striae
Easy brusing
Proximal myopathy
What are the expected levels (high/low) for the following disease for ACTH, Cortisol, High dose DST, MRI?
Cushing’s disease Ectopic ACTH Adrenal adenoma Adrenal carcinoma Iatrogenic glucocorticoids Primary adrenal insufficiency Secondary adrenal insufficiency
Cushing’s disease - ACTH normal/high, Cortisol high, DST suppressible, MRI adenoma
Ectopic ACTH - ACTH high, cortisol high, DST not suppressible, MRI NAD
Adrenal adenoma - ACTH low, cortisol high, DST N/A, Adenoma
Adrenal carcinoma- ACTH low, cortisol high, DST N/A, carcinoma
Iatrogenic glucocorticoids - Low/undetectable ACTH, cortisol low/undetectable, urine cortisol high
Primary adrenal insufficiency - ACTH high, cortisol low
Secondary adrenal insufficiency - ACTH low/Normal, cortisol low
Which drug can induce Cushing’s syndrome?
ARVT in HIV
What changes do you expect with Renin and Aldosterone in:
- primary hyperaldosteronism e.g. bilateral adrenal hyperplasia 60%, Conn’s 35%, familial hyper, pure aldos producing adenoma
- secondary hyperaldosteronism e.g. renal artery stenosis, diurectis
- apparent mineralocorticoid excess?e.g. exogenous mineralo, cushing’s sydnrome, Licorice, Liddle (activating mutation of collecting tubule sodium channel
1 = renin low, aldosterone high
- Renin high, aldosterone high
- renin low, aldosterone low
Pt has been on zoledronic acid for 3 years or 5 years of alendronate/risedronate. Nest step?
If DEXA -2.5, can cease Tx and DEXA in 2 years
When should you start bisphosphonate on a pt on steroid therapy?
If > 3months duration and > 7.5 mg/d with T score
MOA PTU?
blocks conversion of thyroxine to triiodothyronine in peripheral tissue
does not inactivate existing thyroxine and triiodothyronine stores in circulating blood)
MOA Carbimazole?
a prodrug after absorption and is converted to the active form methimazole. Prevents thyroid peroxide enzyme by couling and iodinating tyrosine residues on thyroglobulin hence reducing the production of T3 and T4 (thyroxine)
Tx of thyroid storm (Thyrotoxicosis crisis)?
Most important management is large amounts of glucocorticoids
IV propanolol to interrupt the physiologic response to excess thyroid hormone
High dose thionamide (PTU or carbimazole) to block new hormone synthesis
Iodide - blocks release of preformed hormones
Iodinated contrast agent, propanolol and corticosteroids to block peripheral conversion of T4-T3
PTU blocks conversion but not carbimazole.
Klinefelters. Genetic mutation, Clinical presentation?
The most common congenital abnormality causing primary hypogonadism.
Most common genotype is 47, XXy, extra X chromosome.
Clinical:
Gynaecomastia
Small firm testes
Behavioural and learning abnormalities
Shy, tall, awkward
Fragile X. Mutation? Clinical presentation?
X-linked disorder.
Most fequent form of inherited intellectual disability.
Caused by decreased or absent levels of fragile X mental retardation protein (FMRP) due to loss of function mutation in the fragile X mental retardation 1 (FMR1) gene located at Xq27.3.
Loss of function caused by unstable expansion of CGG repeat at 5’untranlated region.
Clinical: Long and narrow face Prominent forehead and chin (prognathism) large ears testicular enlargement (vol > 25 ml) Developmental delay Delayed language development ADHD, anxiety and ASD
Benefits of metformin?
Glycaemic efficacy No weight gain No hypos General tolerability Favourable cost
T1DM having elective procedure. Mx of long acting basal insulin the night before?
Halve the dose
MOA of insulin?
Insulin binds to heterotetrameric receptor on the cell membrane of target cells.
Binding results in conformational change of the alpha-subunits that enables ATP binding to the beta subunits intracellular domain.
ATP binding leads to activation of a tyrosine kinase in the beta subunit that autophosphorylates the receptor.
The phosphorylated receptor in turn phosphorylates other protein substrates beginning with insulin receptor substrate 1 and 2.
What is pseudohypoparathyroidism?
A condition associated primarily with resistance to the parathyroid hormone.
Pts have low calcium and high phosphate
PTH is appropriately high due to hypoclacaemia
MOA of Biguanides, sulfonylureas, Thiazoledinediones, DPP-4 inhibitors, GLP-1 analogs
Biguanides
- increase insulin sensitivity, reduces hepatic gluconeogenesis, increases peripheral glucose uptake
Sulfonylureas
- stimulate insulin release from pancreatic B cells
Thiazoledinediones
- bind and activate PPAR-y receptors which contributes to decreasing hepatic gluconeogenesis and increasing peripheral insulin sensitivity
DPP-4 inhibitors e.g. sitagliptin
Inhibit dipeptidyl peptidase‑4 (DPP‑4) thereby increasing the concentration of the incretin hormones glucagon-like peptide‑1 and glucose-dependent insulinotropic polypeptide; glucose-dependent insulin secretion is increased and glucagon production reduced.
GLP-1 analogs - act like human GLP-1, increases insulin and inhibits glucagon
What is the most specific test for the Dx of GH deficiency?
IGF-1 measured in an insulin tolerance test
What is the earliest sign of renal disease n T1DM?
microalbuminaemia
Which hormone is first affected in pituitary apoplexy?
ACTH -> lack of cortisol and features of addisonoian crisis i.e. hypotension, hyponatraemia, hypoglycaemia and hyperkalaemia
Then TSH and LH, FSH
What is the first hormone affected in anterior pituitary adenoma?
Gonadatrophin (LHand FSH) first to fall then
GH then ACTH.
ACTH rarely falls due to an anterior pit adenoma.
If you disconnect the pit from the hypothal (Sx or injury) all releasing anterior hormones are cut off therefore levels will fall.
Prolactin will increase as dopamine inhibition is lost.
How does the hypothalamus control the ant and post pituitary?
Anterior pit by means of hormones
Post pit by direct nerve stimulation (neurohypophysis)
What is Sheehan’s syndrome?
A post partum infarct of the pituitary that results in anterior hypopit and sometime affects the post put causing Central DI.
Suspect in postpartum pt with electrolyte disturbance and low TSH.
Pt with Grave’s disease. FNAC of nodule reveals atypic of undetermined significance (Bethesda category 3). Nodule shows benign sonographic characteristics. Mx?
Total thyroidectomy.
High risk of malignancy.
Thyroid nodule shows atypical cells of undetermined significance (ACUS) or Follicular lesions of undetermined significance (FLUS). Mx?
Repeat FNA in 2-3 months.
If ACUS/FLUS, Sx based on clinical grounds (size, growth, pattern) or molecular testing.
What is the role of the following in Glucose control. Glucagon GH Cortisol Adrenaline GLP-1
Glucagon - promotes gluconeogenesis and glycogenolysis (break down glycogen to glucose)
GH - promotes gluconeogenesis and glycogenolysis (break down glycogen to glucose)
Cortisol - Promotes gluconeogenesis and increases insulin resistance by decreasing translocation of GLUT4 receptors. However it also increases glycogen synthesis (as does insulin)
Adrenaline - reduces awareness to hypoglycaemia and can be explained by decreased sensitivity of B-adrenergic receptors in long standing DM
GLP-1 - incretin, not a hormone e.g. exanatide and liraglutide.
Increases insulin secretion from the pancreas in a glucose dependent manner.
Decreases glucagon secretion from the pancreas by engagement of a specific G-protein coupled receptor.
What is the most common hormone secreted by pituitary adenoma? Followed by..
Prolactin (lactotroph adenomas), 44% Results in hypogonadism in male and females Non- functioning adenomas, 22% Somatotroph (GH) adenomas, 8.6 Corticotroph (ACTH), 1.2
What best explains the MOA of PTH in increasing the serum calcium concentration?
Stimulates the synthesis of 1-alpha hydroxylase in the proximal tubules and thus the conversion of calcidiol to calcitriol (1,25 DH).
Increasing the reabsorption of calcium from the renal tubules leading to increased intestinal absorption, increased bone resorption and decreased renal calcium excretion and increased phosphate excretion.
Hormone profile of premature ovarian failure?
high FSH and low oetrodial
normal LH and 17-OH progesterone
Hormone profile of menopause?
High FSH
Low oestrodial due to negative feedback,
Role of FSH?
Females- responsible for the early growth of follicles (follicle stimulating hormone). Produced by granulosa cells if the ovaries by aromatisation.
Males - maintains the spermatogenic epithelium by stimulating Sertoli cells
Role of LH?
Females - responsible for the final maturation of the ovarian follicles and subsequent oestrogen secretion from them
Males - trophic to the Leydig cells which secrete testosterone into the bloodstream
How do prolactinomas cause ammenorrhea?
Inhibit FSH and LH vis inhibition of GnRH so these hormones are usually low to normal rather than elevated
Congenital adrenal hyperplasia. Defect? Presentation? Dx?
Recessive condition. Defective conversion of 17 alpha hydroxyprogesterone to 11-deoxycortisol ->decrease cortisol -> increase ACTH -> normal cortisol but increase androgens.
Presentation: Females present as: Ambiguous genitalia clitoral enlargement common urethral vaginal orifice Males present as: salt losing adrenal crisis (hypoNa, HyperK andFTT)
Dx: measure 17-hydroxyprogesterone (precursor in the pathway), a substrate for 21 hydroxylase. very high levels is diagnostic.
Then ACTH stimulation test is the GOLD standard -> increased 17-hydroxyprogesterone
Primary hyperparathyroidism, Aetiology? Ix findings?
Parathyroid adenomas or hyperplasia Ix: Elevated PTH Raised plasma and urinary Ca ALP elevated Phosphate reduced
Secondary hyperparathyroidism. Aetiology? Ix findings?
Compensatory hypertrophy of all four glands due to hypocalcaemia (due to CKD or malabsorption)
Ix:
PTH elevated
Ca low or normal
What secretes PTH-related protein? Ix findings?
Secreted by squamous cell tumours, breast and renal tumours
Responsible for 80% of hypercalcaemia in malignancy and acts on same receptors as PTH
Serum Ca raised and PTH low
Steps in thyroid hormone synthesis.
- Iodide trapping by the thyroid follicular cells
- Diffusion of iodide to the apex of cells
- Transport of iodide into the colloid
- Oxidation of inorganic iodide to iodine and incorporation of iodine into tyrosine residues within thyroglobulin molecules in the colloid
- combination of 2 diiodothyrosine (DIT) molecules to form a tetraiodothyronine (thyroxine, T4) or MIT with DIT to for a triiodothyronine (T3)
- Uptake of thyroglobulin from colloid not follicular cell by endocytosis, fusion of thyroglobulin with a lysosome and photolysis and release of T4, T3, DIT and MIT
- release of T4 and T3 into the circulation
- Deiodination of DIT and MIT to yield tyrosine
T3 is formed from monodeiodination of T4 in the thyroid and in peripheral tissues
Steps in Vitamin D synthesis.
Vitamin D3 absorbed from skin, D2 from dietary intake
Converted in liver to Calcidiol, 25- hydroxyvitamin D
Converted in kidney to Calcitriol, 1, 25-dihydroxyvitamin D
Calcitriol causes increased intestinal absorption of Ca, increase bone resorption and decreased renal calcium and phosphate excretion.
Calcitriol mediates its biopic effects by binding to Vitamin D receptor.
Vitamin D binds to RANK on osteoclast inducing bone resorption.
What is the Mx of gestational diabetes?
Insulin for Type 1 and 2 DM.
Metformin - crosses placenta. No evidence it is harmful but not recommended.
Gliblecanide - limited passage to placenta but can cause neonatal hypoglycaemia and therefore not recommended
Antihypertensive recommended in pregnancy?
Methyldopa
ACEI teratogenic
Post pregnancy hyperglycaemia in pt with T1DM. Cause?
Insulin resistance common feature of late pregnancy and is a necessary adaptation to allow provision of maternal nutrients to the growing effects.
What is insulin site lipoatrophy?
Complication associated with all types of insulin and estimated prevalence of 3.6%.
Could lead to erratic insulin absorption
What is the role of adiponectin?
an anti-inflammatory cytokine produced by adipocytes
Enhances insulin sensitivity
In liver, inhibits gluconeogenic enzymes
In muscle, increases glucose tranport and enhances fatty acid oxidation
reduced in metabolic syndrome
Role of Grehlin?
Stimulates recreation of GH, increases food intake and produces weight gain
Most abundant in the gastric funds and levels decrease after eating
Role of Glucagon like peptide 1? AE?
stimulating glucose dependent insulin release from the pancreatic islets
Restores 1st and second phase insulin response to glucose
Slows gastric emptying, inhibit inappropriate post meal glucagon release and reduce food intake
N/V and weight loss
