Endocrine Flashcards
Addison’s
Chronic Primary Adrenal Insufficency
Hormone abnormality: Cortisol & Aldosterone Deficiency
Key Clinical Features: Hypotension, hyponatraemia & hyperkalaemia
(Also Hypoglycemia, Eosinophilia and lymphocytosis
Metabolic acidosis)
Testing: 9am Cortisol & Synacthen test
Cushing’s
Hormone abnormality: Cortisol Excess
Key Clinical Features: Hypertension, weight gain & diabetes
Testing: Dexamethasone suppression test or 24-hour urinary cortisol
Conn’s
Hormone abnormality: Aldosterone Excess
Key Clinical Features: Hypertension & hypokalaemia
Testing:
1. Renin/aldosterone ratio,
2. saline (salt) suppression
3. fludrocortisone suppression test
Causes: primary hyperaldosteronism –> adrenal hyperplasia (65%) and adrenal adenoma (30-35%). ((Strictly speaking Conn’s is primary aldosteronism due to adrenal adenoma))
Mineralocorticoid
Class of steroid hormones characterized by their influence on salt and water balance
The primary endogenous mineralocorticoid is Aldosterone
Progesterone is another important example
Synethetic example: fludrocortisone
Mineralocorticoid inhibitors: Spironolactone and Eplerenone
Beta and Delta Thalassemia are associated with abnormalities to which chromosome?
Chromosome 11.
Alpha Thalassemia is associated with abnormalities to which chromosome?
The alpha globulin chain is coded for by genes on Chromosome 16.
From what molecule is DHEA synthesised and when does synthesis occur?
Dehydroepiandrosterone (DHEA) is a steroid hormone synthesised from cholesterol (via Pregnenolone) by the adrenal glands.
The fetus manufactures DHEA, which stimulates the placenta to form estrogen, thus keeping a pregnancy going.
Production of DHEA stops at birth, then begins again around age seven and peaks when a person is in their mid-20s
Aromatase is key to Estradiol production in the ovaries. How is it made?
The theca cells produce androgen in the form of androstenedione.The theca cells are not able to convert androgen to estradiol themselves. The produced androgen is therefore taken up by granulosa cells.
The neighbouring granulosa cells then convert the androgen into estradiol under the enzymatic action of aromatase.
FSH induces the granulosa cells to produce aromatase for this purpose.
Ovarian Endocrine Function: Theca Cells (follicular structure), Thecal Lutein Cells (small luteal) (luteal structure)
Androgen (Androstenedione) production
Thecal Lutein cells produce progesterone
Ovarian Endocrine Function: Granulosa Cells, Granulosal Lutein Cells (large luteal) (luteal structure)
Convert androgen to estradiol via aromatase
Granulosa Lutein cells produce progesterone
Role of LH
LH stimulates Androgen production in the theca (interna) cells
LH also stimulates the contraction of the smooth muscle cells of the theca externa. This increases intrafollicular pressure which results in rupture of the mature oocyte.
Role of FSH
FSH stimulates Aromatase production in the granulosa cells
Glucagon
where is it produced
when is it produced
what does it stimulate/ inhibit
stimulants
inhibitors
Produced by alpha cells
when there is LOW plasma glucose (increases it)
stimulates glycogenolysis and gluconeogen
inhibits glycolysis
stimulants:
Hypoglycemia
Epinephrine
Arginine
Alanine
Acetylcholine
Cholecystokinin
inhibitors:
Somatostatin
Insulin
Uraemia
Increased free fatty acids and keto acids into the blood
Which major hormone of pregnancy is produced by the placenta from 16-hydroxydehydroepiandrosterone sulfate (16-OH DHEAS)?
The placenta produces Estriol from 16-OH DHEAS. Estriol is the major oestrogen (estrogen) of pregnancy and the placenta is the primary site of production.
Pregnenolone is synthesised by the placenta from cholesterol and this is converted to dehydroepiandrosterone (DHEA) in the fetal adrenal gland
Definition: precocious puberty
The development of secondary sexual characteristics at <8 years of age.
Delayed puberty definition
The absence of testicular development (or a testicular volume lower than 4 ml) in boys beyond 14 years old or
by the absence of breast development in girls beyond 13 years old
Testosterone Binding
70% testosterone bound to SHBG
25-30% testosterone bound to albumin
Typical laboratory reference ranges are Male 1.5-3% and female approx 1%.
Causes of Low Sex Hormone Binding Globulin
As a general rule conditions leading to weight gain will lead to a drop in SHBG.
Androgens (inc anabolic steroids)
PCOS
Hypothyroidism
Obesity
Cushing’s syndrome
Acromegaly
Causes of High Sex Hormone Binding Globulin
Oestrogens e.g. oral contraceptives
Pregnancy
Hyperthyroidism
Liver cirrhosis
Anorexia nervosa
Drugs e.g. clomid, anticonvulsants
At ovulation the surge in LH causes rupture of the mature oocyte via action on what?
The luteinizing hormone (LH) surge during ovulation causes:
(1) Increases cAMP resulting in increased progesterone and PGF2 production
(2) PGF2 causes contraction of theca externa smooth muscle cells resulting in rupture of the mature oocyte
Autosomal Dominant Conditions
FAP
MEN
Neurofibromatosis
Noonans
Von Willebrand
Von Hippel Lendea
Autosomal Recessive Conditions
Congenital Adrenal Hyperplasia
Tay Sachs
Cystic Fibrosis
Glycogen Storage Disease
Thalassemia
Haemochromatosis
Sickle Cell
X-Linked Dominant
Fragile X
Rett Syndrome
Vitamin D resistant Ricketts
X-Linked Recessive
Alport Syndrome
G6PD deficiency
Haemophilia
