Endocrinology Flashcards
Where are ADH and oxytocin synthesised?
Hypothalamus
Where are ADH and oxytocin stored?
Posterior Pituitary
What stimulates glucagon?
Hypoglycemia
Epinephrine
Arginine
Alanine
Acetylcholine
Cholecystokinin
What inhibits glucagon?
Somatostatin
Insulin
Uraemia
Increased free fatty acids and keto acids into the blood
What do islet cells produce?
Alpha cells secrete glucagon
Beta cells secrete insulin
Delta cells secrete somatostatin
Gamma cells secrete pancreatic polypeptide
What inhibits TSH?
Somatostatin
(T3 is predominant inhibitor of TSH)
What hormones are produced by the medulla of the adrenals?
Epinephrine
Dopamine
Norepinephrine
What is produced by the zona glomerulosa?
Aldosterone
What is produced by the zona fasciculata?
Cortisol
What is produced by the zona reticularis?
Androgens
What is a typical FBC finding in Addison’s disease?
Eosinophillia and lymphocytosis
What hormones does somatostatin inhibit?
Insulin
Gastrin
Cholecystokinin (CCK)
Secretin
Motilin
Vasoactive intestinal peptide (VIP)
Gastric inhibitory polypeptide (GIP)
Enteroglucagon
Which dopamine agonists may be used to inhibit milk production, and which receptors do they act on?
Cabergoline + bromocriptine
Both act on D2 receptors
In what proportion of children does delayed puberty occur?
3%
What are 2 recognised galactagogues (stimulators of milk production)?
Dopamine Antagonist
1. Domperidone
2. Metoclopramide
Amount of maternal flow through the uterine artery at term?
750ml/min
Amount of flow through the uterine artery when not pregnant?
45ml/min
What are the 3 types of oestrogen?
Estrone (E1)
Estradiol (E2)
Estriol (E3)
What is the predominant oestrogen during female reproductive years?
Estradiol E2 (except in the early follicular phase when estrone predominantes)
What is the predominant oestrogen during pregnancy?
Estriol E3
Which drugs can cause an increased prolactin?
Opiates
H2 antagonists e.g. Ranitidine
SSRI’s e.g. Fluoxetine
Verapamil
Atenolol
Some antipsychotics e.g risperidone and haloperidol
Amitriptyline
Methyldopa
What are the ratios of testosterone free:albumin-bound:SHBG-bound
1% free: 19% albumin-bound: 80% SHBG-bound
Which cells are responsible for androgen production in the ovary?
Theca cells
Which cell are responsible for aromatisation of androgens into oestrogen?
Granulosa cells
Where are the juxtaglomerular cells located?
Afferent arteriole in the kidney
What is the most common cause of delayed puberty?
Constitutional delay
What is the definition of puberty in women?
Physical maturation whereby the women becomes capable of sexual reproduction
What is the lifespan of the corpus luteum?
14 days
How many hours after the LH surge does ovulation occur?
24-36 hours
Where is calcidiol produced?
Liver
During pregnancy, from where is bHG produced?
Syncytiotrophoblast
What tumour marker is used for granulosa cell tumours?
Inhibin
What are the features of hyperaldosteronism?
Hypertension
Hypokalaemia
Alkalosis
What are the causes of primary hyperaldosteronism?
- Unilateral adrenocortical adenoma - Conn’s syndrome (most commonly)
- Bilateral adrenal hyperplasia
What is the cause of secondary hyperaldosteronism?
Renal artery stenosis
What are the laboratory findings in Addison’s disease?
Hyperkalaemia
Hyponatraemia
How is Addison’s disease diagnosed?
Short ACTH stimulation test (i.e. the synacthen test)
What is the first catecholamine to be produced in the synthesis of catecholamines?
Dopamine
From what are catecholamines derived?
Tyrosine (the amino acid)
What blood finding is found in phaeochromocytoma?
Hyperglycaemia
Diagnosis of phaeochromocytoma is with 24-hour collection of urinary catecholamine - but which one?
Vanillylmandelic acid
What is an insulin antagonist?
Somatostatin
What are the physiological effects of progesterone?
- Increased respiratory drive
- Reduced bowel motility
- Increased basal body temperature
What endocrinological manifestation gives rise to the clinical manifestation of PCOS?
Elevated insulin - it is thought to be the insulin that stimulates androgen secretion
At what age is menarche considered precocious puberty?
If occurs prior to age 10
How frequently does GnRH pulse?
Every 90 minutes
What is the overall function of insulin?
Decreased gluconeogenesis
What is the function of GH?
Stimulate lipolysis
What hormones is GH structurally similar to?
Prolactin
hPL
Is plasma iodine concentration reduced or increased during early pregnancy?
Reduced
signaling mechanism involving releasing hormone from cells to acto on another cells
paracrine
percentage of pregnancies complicates to gestational diabetes mellitus
1-5%
earliest gestational age at which the fetal endocrine system is thought to be fully functioning
10 Weeks
Hyperplasia and hypertrophy of alveolar in the breast during pregnancy are stimulated by which hormone?
Prolactin and Human Placental Lactogen
Hormones secreted by endocrine tissue of pancreas
- Insulin
- Somatostatin
- Gastrin
- Glucagon
- Vasoactive intestinal peptide
- Pancreatic Polypeptide
Hormone that regulates apetite and is important in obesity
Leptin
he arterial blood supply of adrenal gland
comes from three sources:
the inferior phrenic artery
the renal artery
the aorta.
Venous drainage of adrenal gland
directly into the inferior vena cava on the right side
into the left renal vein on the left side
Lymphatics drainage of Adrenal Gland
medially to the aortic nodes.
Most important factors of Aldosterone secretion
- the renin–angiotensin system
- changes in the plasma Na+/K+ concentration.
Function of Aldosterone
Aldosterone accounts for 90% of mineralocorticoid activity.
This hormone promotes Na+ reabsorption and K+ excretion by the renal tubular epithelial cells of the collecting and distal tubules
Epinephrine and smaller amounts of norepinephrine are synthesised by, and secreted from
Chromaffin cells of adrenal medulla
The rate-limiting step in the synthesis of catecholamines
is that catalysed by tyrosine hydroxylase, converting tyrosine to 3,4 dihydroxyphenylalanine (DOPA).
Cortisol main actions
- Gluconeogenesis
- Catabolic effect (reduce protein stores)
- Anti inflammatory effect
a. reduce fever
b. reduce phagocytic action of WBCs
c. reduce allergic reaction - Promote normal cell metabolism
- Lipolysis (fat cell breakdown)
- Suppress Immunity
Enhanced release of cortisol can be caused by
▪ Physical trauma
▪ Infection
▪ Extreme heat and cold
▪ Exercise to the point of exhaustion
▪ Extreme mental anxiety
Action of Catecholamines on target tissue is through
G-protein-linked membrane receptors.
These receptors are classified as alpha-adrenergic or beta- adrenergic receptors
Function of Catecholamines
B-adrenegic effect:
+HR
+BP
+SV
dilation of bronchi
mobilization of glucose
++ Lipolysis
alpha-adrenergic effect:
Reduce blood flow to splanchnic bed d.t. VC of arterioles, to divert blood to skeletal muscles
Difference between Cushing syn. and Cushing disease
Cushing syndrome is used for an excess of glucocorticoids, however produced.
Cushing’s disease is used when the excess of glucocorticoids is attributable to an ACTH-secreting pituitary tumour.
Causes of Cushing syn. are broadly divided into 2 types:
✓ ACTH dependent disease: excess ACTH from the pituitary (Cushing’s disease), ectopic ACTH-producing tumours or excess ACTH administration.
✓ Non-ACTH-dependent: adrenal adenomas, adrenal carcinomas, excess glucocorticoid administration.
The most common cause of Cushing’s syndrome is
steroid treatment.
The most common endogenous cause of Cushing syn. is
Pituitary adenoma and this is referred to as Cushing’s disease.
Screening tests for Cushing syndrome include
❑ Measurement of 24-hour urinary levels of free cortisol.
❑ Measurement of midnight levels of salivary cortisol.
❑ Low-dose dexamethasone suppression test.
The definitive treatment for Cushing syndrome
The definitive treatment for Cushing syndrome is surgery. This includes trans-sphenoidal surgery for pituitary disease and adrenalectomy (either laparoscopic or conventional) for adrenal disease.
What is conn’s syndrome?
1ry Aldosteronism
An excess of mineralocorticoid steroids results in Na+ retention in the kidney with loss of K+.
Na+ retention promotes H2O retention and expansion in the extracellular volume, resulting in hypertension and a suppression of renin production.
Causes of 1ry Hyperaldosteronism
▪ Adrenal adenoma (accounting for 80% of the total incidence)
✓Solitary adenoma (65–70%)
✓Multiple adenomas (13%)
✓Micro-adenomatosis (6%)
▪ Adrenal gland hyperplasia (20%)
▪ Adrenal carcinoma (less than 1%)
Causes of 2ry Hyperaldosteronism
Secondary hyperaldosteronism is due to increased renin production in conditions
such as renal artery stenosis or a renin producing tumour
Classical features of conn’s disease
hypertension, hypernatremia, hypokalaemia and hypocalcaemia.
Treatment of 1ry aldosteronism
- 75-90% Adrenalectomy will corrects HTN and hypokalemia
- Mineralocorticoid antagonist (Spironolactone) used but has esterogenic like effects (gynecomastia - impotence)
-Eplerenone is a selective anti-aldosterone agent, which is a specific aldosterone receptor antagonist that does not have the additional antiandrogen effects associated with spironolactone.
What is Addison’s disease
due to 1ry adrenal insufficiency
but it can also be secondary to pituitary damage and results in deficient production of hormones by the adrenal cortex.
Biochemical Features of Addison’s disease
hyponatraemia, hyperkalaemia and hypercalcaemia.
Testing of addison’s disease
9am Cortisol & Synacthen test.
The thyroid gland synthesises and secretes three hormones:
▪ Follicular cells produce thyroxine (T4) and triiodothyronine (T3)
▪ C cells produce calcitonin
Estimates of average normal secretion for euthyroid humans are
- about 100 micrograms/day of T4
- 10-20 micrograms/day of T3
Deficiency of thyroid hormones in fetal, neonatal, and early childhood stages of development can result in
impaired neuropsychological function and impaired growth.
The most severe effects are caused by in utero deficiency, which leads to cretinism.
Maternal thyroid function is modulated by three factors:
- Increase in the concentration of human chorionic gonadotrophin (hCG), which stimulates the thyroid gland.
- Increase in urinary iodide excretion, resulting in a fall in plasma iodine concentration.
- Increase in T4-binding globulin during the first trimester, resulting in increased binding of T4
Why Serum concentrations of T4-binding globulin increase in pregnancy
due to the effects of estrogen.
As a result, the serum concentrations of total T3 and T4 are elevated between weeks 6 and 12 of gestation, stabilising by mid-gestation
Range of T3, T4 and TSH in pregnancy
▪ The serum concentrations of total T3 and T4 are elevated between weeks 6 and 12 of gestation, stabilising by mid-gestation.
▪ The concentrations of free thyroid hormone remain within the normal range for non-pregnant women, although they tend to decrease by 10–15% in late pregnancy.
▪ During the first trimester, serum TSH values decrease slightly in response to elevations in hCG and its intrinsic thyroid-stimulating activity.
Fetal TSH and T4 are first detectable at
week 10 of gestation
Inhibin is secreted by which cell type of the ovary?
Granulosa cells
Which hormone prevent regression of corpus luteum?
hCG
What type of compound is Beta-hCG?
Glycoprotein
Premenopausal estrogen is mainly produced by which cells?
Ovarian Granulosa cells
Precursor of testosterone in theca cell is ?
Androstenedione
Which test you is used to check ovarian reserves in pre-menopausal women ?
Anti mullerian hormone
Which is the most common cause of the premature ovarian failure?
Idiopathic
What hormone secreted by placenta leading to fetal diuresis ?
Vasopressinase
Which of the following placental hormones helps ensure adequate fetal nutrition?
hPL
Pregnant women, in the second or third trimester, may develop diabetes insipidus due to excessive placental elaboration of ?
Vasopressinase
Most common endocrine disorder in reproductive age group ?
PCOs
Addison’s Disease
Chronic Primary Adrenal Insufficency
Hormone abnormality: Cortisol & Aldosterone Deficiency
Key Clinical Features: Hypotension, hyponatraemia & hyperkalaemia
Testing: 9am Cortisol & Synacthen tes
Cushing Syndrome
Hormone abnormality: Cortisol Excess
Key Clinical Features: Hypertension, weight gain & diabetes
Testing: Dexamethasone suppression test or 24‐hour urinary cortisol
Conn’s Syndrome
Hormone abnormality: Aldosterone Excess
Key Clinical Features: Hypertension & hypokalaemia
Testing: Renin/aldosterone ratio, saline (salt) suppression or fludrocortisone
suppression test
Which major hormone of pregnancy is produced by the placenta from 16 -hydroxydehydroepiandrosterone sulfate (16‐OH DHEAS)?
Estriol E3
Which of the following hormones stimulate ductal morphogenesis during pregnancy
Oestrogen and GH
(Alveolar morphogenesis is under control of Progesterone, Prolactin and hPL.)
Polycystic ovarian syndrome is classed as?
WHO type II Ovulation Disorders
The conditions associated with increased risk of pheochromocytoma are:
MEN type 2
Paraganglioma syndromes types 1,3 and 4
von Hippel‐Lindau VHL
Neurofibromatosis type 1
In girls what is the first sign of puberty?
Breast Development (thelarch)
Which is responsible for the formation of Angiotensin I from Angiotensinogen
Renin
According to NICE, diagnosis of GDM is
FBS should be 5.6 and above
2 hrs Postprandrial should be 7.8 and above
Peak maternal serum hCG concentraQons occur a
10 weeks
What percentage triiodothyronin (T3) is free?
1%
Which is non-ergot dopamine agonist drug used to treat hyperprolacQnemia?
Quinagolide
Which of the following hormones increases the excreQon of calcium in Kidney?
Calcionine
When Choriocarcinoma metastasises, it has a propensity for which type of spread?
Hematogenous
Which substance removed from proinsulin to release insulin into the circulation?
C-peptide
Via which paZern of inheritance is the Phenylketonuria
autosomal recessive
Which is the most active form of vitamin D?
1, 25 dihydroxycholecalciferol (calcitriol)
In the developing foetal testis, the cells that produce mullerian-inhibiting
substance are the
Sertoli cells
Peptides cross the placenta by:
active transport
What is the most common cause of secondary hyperparathyroidism?
Chronic renal failure
what percentage of T4 is free
0.1%
LH and FSH half life
LH: 20 minutes
FSH: 4 hours
Iodine accumulation in thyroid cells involves symport with
Sodium
Active form of vitamin D is produced in which organ
Kidney