Endocrine Flashcards
1
Q
What are the three types of hormones?
A
Steroid (all from cholesterol)- cortisol, estrogen
peptide (prohormones that need to be cleaved) - insulin
and amine hormones- from tyrosine ie thyroxine, adrenaline
2
Q
What is the order of action of these hormones in hypoglycemia?
Noradrenaline, growth hormone, glucagon, cortisol
A
N G C G
Norad
Glucagon
Cortisol
Growt hormone
3
Q
What is common about TSH/LH/FSH/bHCG?
A
They all share the same alpha subunit
4
Q
What is the average height growth during puberty?
A
30cm (think a ruler)
5
Q
How do you calculate mid parental height?
A
for girls: maternal height in cm + (paternal height minus 13cm) divided by 2.
for boys: paternal height in cm + (maternal height plus 13cm) divided by 2.
6
Q
What syndromes are associated with short stature?
A
Turners, Russel Silver, Down’s syndrome, Prader Willi
Also achondroplasia, mucopolysaccharidoses (severe short stature in Morquio syndrome)
7
Q
What are three endocrine causes for short stature?
A
Hypothyroidism, Growth hormone insufficiency and cushings
8
Q
What is the definition of constitutional short stature? How do you confirm diagnosis?
A
In teenage boys- delayed growth and puberty.
CONFIRM DIAGNOSIS with delayed bone age
They reach their genetic potential but later. Can give testosterone to kickstart process if really required
This is different to familial where they are short because family is short.
9
Q
When do boys and girls growth plates close?
A
Boys close at 15-17cm
Girls close at 13-15cm
10
Q
What are the investigations for short stature?
A
FBC/UEC/LFT
THyroid
Coeliac
Karyotype in females!
IGF-1 and IGF-BP3 levels.
Bone age
PTH/Ca/Mg/Phos
11
Q
When should short stature be referred?
A
If height is less than 3 standard deviations below mean OR 6cm below 3rd centile
12
Q
What is clinodactyly?
A
Curving of the finger, usually fifth finger.
Present in Downs syndrome commonly, also Russel Silver
13
Q
What is important to measure in a patient with Turners prior to commencing hormones to intiate puberty?
A
FSH! (NOT BONE AGE)
Do this to confirm there is gonadal failure. If no FSH, need ultrasound to make sure gonads are present.
14
Q
What are causes of advanced bone age from an endocrine perspective? (6)
A
Everything up
1. Hyperthyroidism
2. Hyperpituitarism
3. Cushings
4. Precocious Puberty
5. Adrenal pathology (hyperplasia)
6. Intracranial lesions ie astrocytoma
15
Q
What are syndromic causes of advanced bone age?
A
McCune-Albright syndrome (due to precocious puberty), Sotos syndrome, Beckwidth-Wiedeman syndrome, Homocystinuria, Kleinfelters
16
Q
What chromosomal disorders or syndromes cause tall stature? (Think overgrowth)
A
Kleinfelters, Marfans, Sotos, Homocystinuria
17
Q
What are 3 endocrinological blood investigations for tall stature?
A
IGF-1, GH and TFTs.
Then look into sex hormmones etc
18
Q
Which syndrome has ectopia lentis? (Marfans vs Loeys Dietz vs homocystinuria)
A
Marfans and Homocystinuria
Marfan people eat ectopic lentils UPWARDS
19
Q
What is one distinguishing feature between Marfans and LoeysDietx
A
LD= bifid uvula
Marfans= high arched palate.
20
Q
Which one has higher risk of early aortic dissection? (From Marfans and Loeys Dietz)
A
Loeys Dietz
21
Q
Where is ectopia lentis in Marfans vs Homocystinuria?
A
UP in Marfans
DOWN in Homocystinuria
‘Marfans eat UP ectopic lentils’
22
Q
Difference between Marfans and Homocystinuria?
A
Ectopia lentils- UP in Marfans, DOWN in Homo
Also Homo has intellectual dsability (think, takes a lot of brain power to pee)
23
Q
What are the 3 syndromes with Marfanoid presentations?
A
Loeys Dietz- bifid uvuala
Homocystinuria- DOWN ectopia lentis
Shprinzen-Goldberg syndrome- milder symptoms but also has craniosynostosis and intellectual disability
24
Q
What are clinical features of Sotos syndrome?
A
Overgrowth syndrome. Aut dom
BW and length >90th centile
Excessive height velocity in first few years. Large hands and feet
25
What are the three treatments for congenital hyperinsulinism?
Diazoxide: cause hirsutism, oedema and nausea
Somatostagin analouge ie octreotide. Causes growth disturbance, hepatitis, necrotising enterocolitis
Sirolimus
Total pancreatectomy
26
What are the two factors controlled primarily by hypthalamus?
Temperature and appetite
Appetite via leptin and Ghrelin
27
Where is the origin of the anterior vs posterior pituitary>
Anterior- from oral ectoderm
Posterior- neural ectoderm
28
What is released in ant pituitary
ACTH, GH, LH, FSH, TSH, prolactin
29
What is released in posterior pituitary?
Oxytocin and ADH
30
Where is Growth hormone released from and where does it act?
Released from anterior pituitary, acts on liver to make IGF-1.
31
What is the PATTERN of secretion for growth hormones
Pulsatile secretion with peaks and troughs. Steady increase in childhood, PEAK in puberty and augmented by sex hormones.
32
What are the 3 main hormones involved in control of GH secretion?
GHRH, ghrelin and somatostein.
(Ghrelin released by stomach when hungry)
33
What do LH and FSH do for males ?
LH: Leydig cells to cause production of testosterone. 5a redustase converts to hidydrotestosterone
FSH: Sertoli cells for Sperm production
34
What do LH and FSH do for females
LH: bind to ovarian cells and stimulates steroidogenesis ie ANDROGENS
FSH: binds to glomerulosa cells and stimulates conversion of testosterone to oestrogen (By producing aromatise)
35
How are LH and FSH secreted or triggered?
Pulsatile GnRH secretion.
HIGH at birth, low in childhood and nightime increase leading up to puberty
36
How is TSH secretion regulated from pituitary>
TRH from hypothalamus, goes to pituitary for TSH.
37
What is the action of ACTH?
Stimualtes adrenal cortex, esp cortisol. Important in foetal adrenal growth.
CRH stimualtes ACTH (corticotrophin releasing hormone,)
38
How is the regulation of vasopressin done?
Through detection of serum osmolality
39
What does ADH do?
Insertion of acquaporin into collecting ducts to allow urine sodium concentration
40
What is the presentation for septo-optic dysplasia?
Optic nerve hypoplasia
Absence of septum pellucidum and/or corpus callosum AND pituitary deficiency (commonly growth hormone def)
41
What is a common deficiency or problem post treatment of a craniopharyngioma?
Hormone def in anterior and posterior pituitary
42
What does a craniopharyngioma present with?
Rememeber remnant of Rathke's pouch.
Presents with headaches and visual field disturbance
43
What is the definition of diabetes insipidis? Where does the condition origin?
Posterior pituitary OR nephrogenic disorder and due to insufficient ADH secretion leading to polyuria and polydipsia.
44
How can you decompensate in diabetes insipidus?
So, if can drink copius amounts of water (thirst intact) then nil issues and can maintain osmolality despite excessively dilute urine.
If no thirst --> HyPERnatremic dehydration
45
In diabetes insipidis, what happens if there is a concurrent anterior pituitary dysfn? (Think ant pituitary hormones)
Cortisol needed to secrete water so if not present, and giving vasopressin, will get dilutional hyponatraemia.
Solution is to increase hydrocort and stop DDAVP (vasopressin)
46
What are some central causes of diabetes insipidus
Think of all the things affecting POSTERIOR pituitary ie
Craniopharyngioma, germinoma, langerhan cell histiocytosis, trauma, serp-optic dysplasia.
47
What is A renal cause of daibetes insipidis>
X linked nephrogenic diabetes insipidus, secondary to renal damange
48
How to differentiate between psychogenic polydipsia and diabetes insipidis?
Psychogenic: will have dilute urine during the day (because drinking water) but first morning urine should be normal osmolality as not diluting from drinking water and has normal functioning kidney and ADH.
49
What is SAIDH?
Water retention due to inappropriate ADH
50
What are some causes of SIADH?
head: meningitis, abscess, HIE
lungs: Pneumonia, cavitation
malignancies: lymphoma, bronchogenic carcinoma, idiopathic
51
What is the treatment for SIADH?
Fluid restriction
52
What are the steps for a water deprivation test and what is it sued for?
Used to diagnose diabetes insipidis.
1. Weight and deprive water for max 7 hours
2. Mointor urine osmolality hourly
3. Plasma sodium and osmolality 2 hourly
STOP test if:
1. Weight falls by >5%
2. Serum osmolality >300 with inappropriate dilute urine <300
3 Clincially unwell.
If can progress, give DDAVP once plasma osmolality >300 and measure.
If urine osmolality >300, then central DI otherwise nephorgenic.
53
What is the difference between central and nephrogenic DI?
Central= absence of ADH
Nephrogenic= insensitivity to ADH
54
What causes release f LH and FSH from pituitary
GnRh
55
Mechanism by which steroids cause neutrophilia?
Neutrophil diapedesis (adhesion to and migration through the vascular endothelium) and chemotaxis (migration to the site of inflammation) is severely impaired by glucocorticoids, particularly when given at high doses. This increases the number of circulating neutrophils, as they are unable to move from the intravascular space.
56
What is the difference between primary and secondary sexual characteristics?
Primary= genital growth, gonadal development and function, spermatogenesis and menses
Secondary= everything else, measured on Tanner scale is pubic hair, body odour, voice change, breast development
57
What are the pubertal stages for females?
TPM
Thelargic
Pubarche (same as adrenarche)
and Menarche
58
What is the order of puberty in males?
TPP (because boy always need to pee)
Testicular enlargement, penile growth, pubic hair growth, peak height velocity and sperm.
Easier to visualise.
59
Which hormone is important for breat development and growth acceleration? What causes fusion of growth plates in a short period of time from increased secretion
Estrodiol
60
When is mini puberty?
1-2 months, high FSH and LH but no peripheral effets
61
What causes regression of the mullerian ducts? What cells secrete it?
Sertoli cells release AMH which causes regression
62
Which cells do FSH act on in females?
GranuloSA cells.
fSh, loSa..
63
What is the definition of precocious puberty?
<2.5std from mean.
<8 in girls and <9 in boys
64
What are the 3 categories of causes for causse of precocious puberty?
Central, peripheral and benign/non-progressive periphearl variants
65
What are central causes of precocious puberty? What is the most common cause?
MOST COMMON = benign hypothalamic haemartomas
Others are tumours in CNS, malformation, irradiation
66
What are peripheral causes of precocious puberty
Adrenal, ovarian, testicular tumours, McCUne Albright syndrome leading to EXCESS steriod production.
So increased testosterone and estadiol with reduced LH and FSH due to feedaback
67
What is the most common deficiency from intracranial surgery?
Growth hormone def
68
What is the gold standard test for precocious puberty?
GnRH stimualtion test. Measure maximal LH levels post GnRH
69
What are 5 features of McCUne Albright syndrome?
1. Precocoious puberty (excess sex steroids)
2. Coast of main lesions
3. bony fibromas
4. Pigmented skin lesions
5. Thyroid, adrenal and pituitary over secretion
70
Treatment for central precocious puberty?
Problems coming from GnRH oversecretion so BLOCK it, leading to reduced LH and FSH.
Treatment can help avoid potential height loss
********************
LUCRIN= GNRH agonist. So initially causes rise in oestrogen and testosterone production but long term use= cessation leading to final effect.
71
Treatment for peripheral causes of precocious puberuty>
Aromatase inhibitors (stops conversion of testosterone into oestrogen)
72
What are pathological causes of gynaecomastia?
Marijuana, hypogonadism (XXY) and sex steroid releasing tumours
73
What is the definition of delayed ouberty in boys vs girls?
Boys 14
Girls 13
74
What are causes of delayed puberty? Nb 4 categories
Hypothalamus: lesions interfering with GnRH
Pituitary: Craniopharyngioma, traume, SEPTO_OPTIC DYSPLASIA, Kallman syndrome
Constitutional
Gonadal: trauma, cryptorchidism, XXY, chemo
75
What are the 3 characteristic features of Kallman syndrome?
cleft palate, anosmia and pubertal delay secondary to hypogonadotrophic hypogonadism
'Kaali maa destroys the sense of smell'
76
What gene is required to make a testes in embryogenesis?
SRY and Sox9
77
What hormone is essential for internal vs external structures in males?
Dihydrotesto for external male genetalia
Testosterone for internal wolfian structures
78
What is the difference between Wolfian and Mullerian strcutures?
Wolfian= for males.
Mullerian= for females
79
What is the cardiac anomaly in Turners?
Bicuspid aortic valve
80
What tumour can form in 46XY or 46XX with DSD?
Gonadoblastoma, may need gonaedtomy (oophorectomy)
81
What syndrome causes complete gonadal dysgenesis in the context of male DSD?
Swyer syndrome
If you are not a male, you are a sewer
82
What is the difference between mullerian agenesis and androgen insensitivity syndrome?
BOTH HAVE AMENORRHOEA but, androgen insensitivty will have testes. They responded to AMH but not to testosterone for external differentiaion
83
What is the presentation of aromatase def?
Remember, need aromatase to convert testosterone to estradiol.
So def = ++ testosterone = ambigious female genetalia ie clitoromegaly and scrotolisation of labia
84
What is the MOST important condition to rule out in presentation of a DSD?
CAH.
85
What are the three layers of the adrenal gland? Going from out to in?
GFR
Glomerulosa
fasciculata
Reticularis
86
What do the three layers of adrenal gland produce?
GFR (layers) and MSA going out to in
Minerelocorticoids
Steroids (*F steroids)
Androgens (secret so keep them inside)
87
What is the main function of aldosterone?
INCREASE sodium reabs from urine/sweat etc
WASTE potassium and hydrogen
This is why you get hyponatraemia and hypokalemia and met acidosis in Addisons
88
What is aldosterone regulated by?
Renin-angiotensin system
89
Why is there no salt wasting in 11betahydroxylase def?
Still production of deoxycorticosterone which has mineralocorticoid effect
90
What system regulates glucocorticoids?
Hypothalamic pituitary axis
91
What are the main adrenal androgens?
DHEAS- give rise to adrenarche
Responsible also for EXTERNAL puberty features in males which is why you get it with adrenarche
92
What are causes of PRIMARY adrenal insufficiency
Problem in adrenals so HIGH ACTH but nothing from the adrenals
CAH
Autoimmune adrenalitis
Adrenoleukodystrophy
Adrenal hypoplasia
Lysosomal/peroxisomal disorders
93
What are secondary causes of adrenal insufficnecy?
LOW ACTH- nothing driving the adrenals to make the steroids
hypopit
hypothalamic tumours
exogenous steroid treatment
94
Where is the mutation in CAH?
Thinks of CAHS
Chromosome 6
Think CAH-S - S for six
95
What is the most common problem in CAH and what is the result?
21hydroxylase def so NO cortisol, NO aldosterone, HIGH progesterone--> testosterone
96
Presentation of CAH
Newborn with FTT, hypotension, vomiting, lethargy and VIRILISATION. Males will have pigmentation of the gonads
97
What is elevated in CAH (bloods wise)
17-OH Progesterone. Androstenedione and ACTH
98
What is the presentation from atypical or late onset CAH?
They have the steroids but symptoms from androgen excess so irregular periods in girls and precocious puberty in boys
99
What is the diagnostic test for CAH?
Think: they can't produce steroids due to enzyme def SO ACTH stimulation test.
(short syancthen)
Give ACTH and measure cortisol and 17OHP at 30 and 60 mins. If 17OHP raised then diagnositc.
100
Treatment for CAH?
Treat with high dose steroids, Fludrocort (mineralocorticoid) and salt. Monitor Renin and BP.
IF HIGH BP AND LOW RENIN, reduce fludrocort.
101
What is the key feature for Addisons' disease (Visually)
Hyperpigmentation
102
What are the top two DDx for Addisons
CAH
Adenoleukodystrophy (look for long chain fatty acids- peroxismal disorder)
103
Treatment for primary and secondary adrenal insufficiency?
Primary:corticosteroid and mineralocorticoid replacement
Secondary: only steroid def so replace that/
104
When should steroids be weaned?
If givenf or 2 weeks.
HPA axis can take uptp 12 months to recover after high dose therapy.
105
What is Cushings syndrome?
Anything that elevates Cortisol! ie ACTH secreting pituitary adenoma, ectopic ACTH secretion, exogenous glucocorticoids, adenocortical tumour
106
Investigations for Cushings syndrome?
Urinary free cortisol- 3 samples
Also midnight salivary cortisol (should be low)
Dexamethasone suppression test: Give 1 mg and is suppressed cortisol in AM,not Cushings
107
What is the reason for giving 1mg vs 8mg of ddexamethasone suppression test?
1mg for cushings
8mg to differentiate between pituitary ACTH or ectopic/adrenal cause. If ACTH, will respond to high dose steroids
108
What is the testing for phaeochromocytoma?
plasma and urine catecholamine
(metanephrine is breakdown for catecholamine)
109
What is the T4 and TSH level in sick euthyroid?
Low T4, normal or raised TSH
110
What is pendred syndrome?
Congenital hypothyroidism from dysghormonogenesis. AR and SSNHL
111
What is the msot common cause of congenital hypothyroidism
Thyroid dysgensis followed by dyshormonogenesis
112
Presentation of congenital hypothyroidism
macrosomina, wide fontanelle, macroglossia, hoarse cry
113
Common finding in ectopic thyroid?
Elevated TSH but low to normal T4
Ectopic uptake on nuclear medicine scan
113
Common finding in ectopic thyroid?
Elevated TSH but low to normal T4
Ectopic uptake on nuclear medicine scan
114
What is the ratio of TSH in NBST vs serum?
TSH in serum double that on the Guthrie
115
What condition will NOT be detected on guthrie?
Panhypopit
Only detects elevated TSH
116
What syndrome is associated with phaeo and hyperparathyroidism?
MENII
117
What is the Dawn phenomenon?
Elevated BSL prior to breakfast secondary to GH ? secondary to combined effect of gluconeogenesis and glycogenolysis.
NO PRECEEDING HYPO unlike Somoyagi
118
What is the Somogyi phenomenon?
Elevated early morning BLS due to EXAGERRATED response to hypoglycemia
119
If a child had T1DM, risk of twin having it? (identical)
50-95%
120
Diabetes risk of sibling or non-identical twin has it?
10%
121
What is DEND syndrome?
Its an acronym with 3 things.
Diabetes= PERMANENT NEONATAL DIABETES
Developmental delay
Epileosy
Treat with sulfonylurea
Different to DENT!!!!!
122
What syndrome causes permanent neonatal diabetes?
DEND syndrome
Dentist syndrome- go to dentist for teeth which are made of calcium. Lots of calcium in Dent ... Have to go to dentist in first place because mouth full of sugar
123
What antibody most commonly associated with T1DM?
GAD-65 (commonly >2yo)
IAA <2
124
What are the top three associations with T1DM ?
1. Coeliac
2. Thyroid
3. Addisons
125
What does alcohol do to hepatic glucoeneogenesis?
Inhibits it
126
What is MODY and which subtypes account for 90% of the cases?
'Monogenic defect diabetes'
monogenic defect in beta cell function
MODY 2,3 and 5 account for 90% of presentation
MODY 3 i 50-65% of cases and often progressive
127
Treatment for MODY
Sulfonulurea
Ex for MDY 5 from HNF beta that gets insulin)
128
Most common deficient hormone post craniopharyngioma surgery?
Vasopressin, and then GH
129
Where does Vitamin D2 come from?
DIET- fruits and vegetables.
Think you eat 2 fruit (vegetables) a day
130
Where does Vitamin D3 come from?
MEAT and the skin
131
What is required to convert pre Vit D3 to D3?
7 dehydrocholesterol
132
What is the activation process for Vit D2 and D3? What enzymes are involved?
D2 and D3 go to liver- 25hydroxylase adds OH group.
And then, they go to the kidneys (PCT) where they are activated by 1a hydroxylase to form active Vit D2 and D3
133
What are the calcium related functions of Vit D (activatedI
Osteoclastic bone resorption
Increased intestinal resorption
Inhibitir pTH secretion and increase 1a hydroxylase
134
What are non calcium relation functions of Vit D (activated)
Decreased renin, activates B and T lyphocytes and maintain normal cell proliferation
135
What is THE active form of Vit D? (the scientific form?
1,25-OH D3
136
How is calcitriol regulated?
Essnetially self regulated.
If hifh, feedback to a1 hydroxylase (stops conversion into active form)
137
What organ produced calcitonin
Thyroid
138
What is the action of calcitonin?
STOPS breakdown of calcium, regulates calcium levels
139
What are the types of Ricketts
There are multiple types.
Calciopenic, Phosphopenic, Vit D dependant (4 of these subtypes), and congenital hypophosphatemic rickets
140
What happens to calcium and phosphate levels with high vit D vs PTH?
Vit D= both calcium and phos increase
PTH only ca incresse. phos low
141
Action of PTH?
Increased bone resorption, also phosphate dumpning in the urine causing hypophosphataemia and rickets
142
What is the most common cause of hypophosphataemia rickets?
(Past exam question)
Renal salt wasting- primary Fanconi OR increased PTH and FGF23.
FGF23 released from bones to stop vitD hydroxylation and phosphate reabs in kidney
Other cases are deitary def OR intestinal malabs from drugs with Mg/chronic diarrhoea
143
What syndrome causes rickets?
X-linked hyphophosphtaemic rickets.
PHEX gene
X-linked DOMINANT
144
What are some XRAY or bone features on presentations with Rickets?
Bowing of legs, ricketic rosary, widened 'moth eaten' growth plate
145
What is measured in the blood in terms of Vit D?
25OHD (the one from liver, NOT from kidney)
calcidiol is the circulating form of cholecalciferol. CalciTRIOL= kidney
146
What is the factor incharge of renal excretion of phosphtae?
Fibroblast growth factor (FGF)-23
147
What is present in hypophosphatasia?
Alkaline phosphatase def- ALP def.
Rachitic chest, respiratory insufficiency, skeletal deformities, hypomineralisation.
148
What can present with nephrocalcinosis and low ALP?
HYPOPHOSPHATASIA
149
How do bisphosphonates work?
Inhibition of osteoclast activity
150
Side effect of bisphosphonate?
hypocalcemia, osteonecrosis of the jaw
151
Symptoms of hyPOcalcaemia?
Abdominal cramos, tetany, paresthesias
152
Which ostegenesis imperfecta (1-7) is lethal?
Type 3
153
Where is parathyroid hormone made? Half life?
In chief cells of the parathyroid, half life of 2 mins
154
Causes of hyPOparathyroidism
1. Absent parathyroid hormone or aplasia
2. DiGeorge
3. APECED
4. Post thyroid surgery
5.CHARGE
6. haemochromatosis
7. Wilsons disease
155
What is pseudohypoparathyroidism?
PTH receptor defect
Low Ca, high phosphate, high PTH and SUPPRESSED calcitrioln
156
What syndrome causes low PTH
DiGeorge
157
What syndrome has hyperparathyroidism as the most common presentation?
MEN 1
158
What syndrome causes low PTH?
Williams syndrome
159
What syndrome causes medullary thyroid cancer?
MEN2A
Together, Men 2A and 2B account for 25% of medually thyroid cancers in childhood
160
What type of cancer in common in MEN Type 1
Pancreatic, mutation in MEN 1 gene
161
What syndrome presents with similar features to Prader-Willi but night blindness?
Bardet-Biedel
Hard to read tales of Beedle and bard. Also have reduced intellect, short stature and hypogonadism
162
What is mode of inheritance for MEN syndormes?
AUT DOMINANT
163
What hormone acts opposite to calcitonin
Parathyroid hormone.
Stops breakdown of bones and also reabs of calcium in kidneys
