Endocrine - Pituitary Disease Flashcards
(156 cards)
1
Q
Where does anterior pituitary get its blood supply?
A
From hypothalamic-pituitary portal plexus via SUPERIOR HYPOPHYSIAL ARTERY
2
Q
What are the subunits of anterior pituitary hormones?
A
Alpha subunit: common to TSH, LH, FSH and hCG
Beta subunit: determines specificity
3
Q
Growth hormone is secreted by which cells in response to what?
A
By somatotrophs in response to GHRH
4
Q
When is GH secretion elevated?
A
Deep sleep
Exercise and physical stress
Trauma
Sepsis
5
Q
When is GH secretion decreased?
A
Obesity
6
Q
What stimulates GH secretion?
A
Ghrelin
Oestrogen
7
Q
What inhibits GH secretion?
A
IGF-1
Chronic glucocorticoids
Somatostatin
8
Q
What is the INDIRECT action of GH?
A
GH stimulates IGF-1 release from liver.
IGF-1 in skeletal muscle and cartilate then increases uptake of amino acids and protein synthesis.
9
Q
What is the DIRECT action of GH?
A
In epithelium: stimulates mitosis
In adipose: stimulates breakdown of fatty acids and cells use fatty acids rather than glucose
In liver: stimulates glucogenolysis
10
Q
How is IGF-1 circulated?
A
IGF-1 is bound to circulating IGFBP the main one is IGFBP3 is GH-dependent
11
Q
Where is IGF-1 synthesised?
A
In the liver
12
Q
What conditions have higher levels of IGF-1?
A
Higher levels in women and puberty
13
Q
What conditions have lower levels of IGF-1?
A
Low in hypocaloric states with GH resistance (ie: cachexia, malnutrition and sepsis)
14
Q
Function of IGF-1?
A
Induces hypoglycaemia, low doses improve with insulin sensitivity
Anabolic
Increased bone turnover
15
Q
Laron’s Syndrome
A
= partial or incomplete GH insensitivity and growth failure
Diagnose with normal/high GH levels but decreased GHBP and IGF-1 levels
16
Q
Clinical features of adult growth hormone deficiency?
A
Body composition changes:
- reduced lean body mass
- increased fat mass
- selective deposition of intra-abdominal fat
- increased waist:hip ratio
Hyperlipidaemia
LV dysfunction
Hypertension
Increased (x3) CVS mortality
Increased fibrinogen levels
Reduced bone mineral density
Increased fracture rates
Depression
17
Q
Diagnosis of growth hormone deficiency?
A
Insulin tolerance test GHRH test Arginine-L dopa test Glucoagon-stimulation test Serum-IGF
18
Q
Causes of Acromegaly from Excess GH Secretion:
A
Pituitary:
- carcinoma
- McCune Albright
- MEN1
Extra-Pituitary:
- pancreatic islet cell tumour
- lymphoma
19
Q
Causes of Acromegaly from Excess GHRH secretion?
A
Central
Peripheral:
- *** medullary thyroid cancer
- bronchial carcinoid
- pancreatic islet cell tumour
- SCLC
- Adrenal adenoma
- pheochromocytoma
20
Q
Clinical features of acromegaly
A
Frontal bossing / increased hand or feet / mandibular enlargement / widened incisors
Soft tissue swelling Hyperhidrosis Deep hollow voice Oily skin Acanthosis nigricans
Arthropathy
Kyphosis
Carpal tunnel syndrome
Proximal muscle weakness and fatigue
Visceromegaly Cardiomegaly and diastolic failure Hypertension Obstructive sleep apnoea Diabetes (>10%)
Increased risk colon cancer and thyroid cancers
21
Q
Risk of which cancers is increased with acromegaly?
A
Colon cancer and thyroid cancer
22
Q
Which clinical feature of acromegaly is irreversible?
A
Arthropathy
23
Q
Diagnosis of Acromegaly?
A
Elevated IGF-1 (screen)
75mg oral glucose challenge: GH SHOULD suppress to 1-2 hours post intake
(** 20% get a paradoxical rise **)
Prolactin is elevated in 25%
24
Q
When should someone with acromegaly get colonoscopies?
A
From age 40yrs
25
Role of surgery in acromegaly?
First line for adenomas
Transphenoidal resection:
- microadenoma remission 70%
- macroadenoma remission <50%
* * swelling improves immediately
* * IGF-1 normalises within 3-4 days
* * GH normalises within an hour
26
Post transphenoidal resection for acromegaly how common is hypopituitarism?
15%
27
Action of somatostatin analogues?
ie Octreotide
Suppress GH secretion by binding to SSTR2 and SSTR5
28
How well does octreotide work in acromegaly?
Normalises IGF-1 in 60%
| Half life is 2hours
29
Side effects of octreotide?
- suppression of GI motility and secretion
(--> diarrhoea, flatulance and fat malabsorption)
- suppresses postprandial gallbladder contractions and delays gallbladder emptying
- mild glucose intolerance
- bradycardia
- hypothyroxinaemia
30
Action of GH-Receptor Antagonists in acromegaly?
ie: Pegvisomat
Blocks PERIPHERAL GH binding to receptor
(and suppresses serum IGF-1_
31
How well does Pegvisomat work in acromegaly?
Normalises IGF-1 in 70%
Does not target adenoma (therefore serum GH will remain high)
32
Side effects of Pegvisomat?
LFT derangement
| Lipodystrophy
33
Action of dopamine agonists in acromegaly?
ie: Bromocriptine and Cabergoline
Only MODESTLY suppresses GH secretinos SOMETIMES
34
Role for radiation in acromegaly?
GH levels reduce over time
50% of people require >8 years to suppress, therefore usually need interim medical treaments
35
What is octreotide?
Somatostatin analogue
36
What is pegvisomat?
GH-Receptor Antagonist
37
What is Bromocriptine?
Dopamine Agonist
38
What is Cabergoline?
Dopamine agonist
39
Prolactin is secreted by what cells?
Lactotrophs
40
When does prolactin secretion peak?
Between 4-6AM during REM sleep
41
What stimulates prolactin secretion?
```
Prolactin Releasing Hormone (PRLH)
Thyrotropin-Releasing Hormone (TRH)
Vasoactive Intestinal Peptide (VIP)
Oestrogen
Oxytocin
```
42
What is the predominant central inhibition of prolactin secretion?
Dopamine D2 receptor
43
Elevated levels of prolactin are seen in...?
```
Post exercise
Meals
Surgery
General anaesthesia
Chest wall injury
Acute MI
```
44
Decreased levels of prolactin are seen in...?
Thyroid hormone
| Steroid use
45
How does prolactin act?
Signals via JAK --> STAT family
Induces and maintains lactation
Decreases oestrogen function
Decreases oestrogen
- -> blocks folliculogenesis
- -> inhibits granulosa cell aromatase
- -> amenorrhoea
Decreases libido
46
Causes of Hyperprolactinaemia?
Pregnancy/Lactation
Physiologic (nipple or sexual organism, sleep or stress)
Prolactinoma
Pituitary:
- stalk disruption or macroadenoma
- lymphocytic hypophysitis
- radiation and trauma
Primary hypothyroidism
Renal Failure
Pharamcologic:
- Antipsychotics (risperidone)
- metoclopramide (inhibits D2 receptor)
- Methyldopa (inhibits dopamine synthesis)
- CCBs (verapamil) block dopamine release
- H2 antagonists
- opioids
- amitryptiline
47
Which drugs can cause high prolactin levels?
- Antipsychotics (risperidone)
- metoclopramide (inhibits D2 receptor)
- Methyldopa (inhibits dopamine synthesis)
- CCBs (verapamil) block dopamine release
- H2 antagonists
- opioids
- amitryptiline
48
How does hyperprolactinaemia present?
Amenorrhoea
Galactorrhoea
Infertility
Visual loss from compression of optic chiasm (Bitemporal hemianopia)
Long term:
- osteopenia
- decreased libido
- weight gain
49
Diagnosis of hyperprolactinaemia
Basal fasting prolactin level
Measure TFTs
MRI
50
Role of dopamine agonists in hyperprolactinaemia?
- suppress prolactin secretion and synthesis
- suppress lactotrope cell proliferation
Once prolactin normal and tumour shrinks
--> Then after two years can withdraw medical treatment **if >50% reduction in size and >5mm from vital structures**
51
What is important monitoring when giving dopamine agonists in hyperprolactinaemia?
Need formal visual fields before treatment 6-monthly until mass shrinks annually afterwards
52
How many patients with hyperprolactinaemia will not respond to dopamine agonists?
20% of patients (especially males) are resistant to dopamine agonists
53
Which are the two dopamine agonists used in hyperprolactinaemia, and how are they different/similar?
CABERGOLINE (Preferred) (ergot-derived)
- suppress prolactin for >14 days
- success in 80% microadenoma, 70% macroadenoma
- side effects less common than bromo
BROMOCRIPTINE (ergot alkaloid)
- short acting
* ** preferred in pregnancy ***
54
Side effects of the dopamine agonists used in hyperprolactinaemia?
Cabergoline and Bromocriptine:
- constipation, dry mouth
- nightmares and insomnia
- vertigo
- auditory hallucinations
- cardiac valvulopathy (CABERGOLINE)
55
Role of surgery in treatment of hyperprolactinaemia?
Surgery if:
- dopamine resistant / intolerant
- compromised vision not improving
30% success for macroadenoma (50% long term recurrence)
70% success for microadenoma
56
Role of radiation in treatment of hyperprolactinaemia?
Only if aggressive and not responding to other treatments
57
Management of prolactinaemia in pregnancy
Microadenoma:
- discontinue dopamine agonist
- periodic visual loss
- repeat MRI 6 weeks postpartum
Macroadenoma:
- consider surgery prior to pregnancy
- ensure BROMOCRIPTINE SENSITIVE before getting pregnant
- Give BROMOCRIPTINE as soon as vision is compromised
OR
continue if vision is already affected
- consider high dose steroids or surgery during pregnancy if vision is threatened or adenoma haemorrhage
- MRI postpartum at 6 weeks
58
Where is ACTH synthesised?
In corticotrophs in anterior pituitary
59
What protein is ACTH derived from?
POMC precursor protein
60
What suppresses ACTH synthesis?
Glucocorticoids
61
What induces ACTH synthesis?
CRH
AVP
IL-6
Leukaemia inhibitory factor
62
What stimulates the secretion of ACTH? And from where?
Stimulated release by CRH from the paraventricular nucleus
63
When does secretion of ACTH peak and trough?
Peak at 6AM
| Trough at midnight
64
What are the ACTH-inducing cytokines?
TNF
IL-1
IL-2
IL-6
65
What is the receptor for ACTH? What type of receptor is it?
Melanocortin-2 Receptor (G-protein coupled receptor)
66
Where is the ACTH receptor? What does it do?
Stimulation of ACTH receptor or ADRENOCORTICOID CELLS in the ZONA FASCICULATA to make glucocorticoids (cortisol and cortisterone)
67
ACTH acts on which zones of the adrenals to stimulate synthesis of what?
Zona glomerulosa --> mineralocorticoids (aldosterone)
Zona fasciculata --> glucocorticoids (cortisol and corticosterone)
Zona reticularis --> adrenal androgens (DHEAS / andostenedione)
68
What are the ACTH-Dependent Causes of Cushing's Syndrome?
Cushing's Disease (pituitary adenoma)
Ectopic ACTH production (ie bronchial carcinoid)
Ectopic CRH production
69
What are the ACTH-Independent Causes of Cushing's Syndrome?
Adrenal adenoma or carcinoma
Micronodular hyperplasia (primary pigmented nodule adrenal disease PPNAD)
Macronodular hyperplasia (ACTH-independent macronodular adrenal hyperplasia AIMAH)
70
What is Primary Pigmented Nodular Adrenal Disease (PPNAD)
- Sporadic PPKAR1A mutation or CARNEY COMPLEX (Autosomal Dominant)
= hyperpigmented + excess endocrine
71
Clinical features of Cushings Syndrome?
Chronic cortisol excess:
- think skin
- central obesity and moon facies
- Hypertension
- plethora
- purple striae >1cm
- easy bruising
- diabetes
- proximal muscle weakness
- osteoporosis ** esp necrosis of femoral head
Hyperandrogenism: acne and hirsutism
Psych disturbance: mania and psychosis
Haem: leukocytosis, lymphopenia and eosinopenia
Hypokalaemic alkalsosis: if K<3.3 more likely ectopic ACTH
Hyperpigmentation
72
Features MOST SUGGESTIVE of Cushings?
Plethora
Purple striae >1cm
Easy bruising
Proximal muscle weakness
73
What are the features associated with an Ectopic ACTH cause of Cushings Syndrome?
- higher ACTH
- Rapid progression
- severe myopathy
- pigmentation
- hypokalaemia
- VERY HIGH cortisol and ACTH
74
Occult ACTH production when causing Cushing's Syndrome is usually the result of what types of tumours?
Bronchial carcinoid
Thymoma
SCLC
75
Screening tests for suspected Cushing's Syndrome?
1) 24 hour urine free cortisol
2) Late night cortisol
- late evening 11pm serum cortisol
if <50nmol/L --> excludes cushings
if >207nmol/L --> is y
- late night/midnight salivary cortisol
3) Overnight 1mg dexamethasone suppression test
- give 1mg at 11-12pm then check morning cortisol between 8-9am. If normal then not Cushings.
76
What are the special populations you need to consider when screening for Cushings Syndrome?
Pregnant: use UFC
Epilepsy: use measured NONSUPPRESSED cortisol
Renal failure: use 1mg overnight dexamethasone suppression test
Cyclical cushings syndrome: use UFC or midnight saliva
Adrenal incidentaloma: use 1mg DST or midnight saliva
77
Which is better, the low dose 0.5mg 6hrly x 8 dexamethasone test or the 1mg dexamethasone suppression test?
Equally as effective
Do 0.5mg 6hrly x 8 times then measure 24 hour urinary cortisol in the 2nd 24 hour period.
78
What further testing do you do once you have confirmed Cushings?
Test ACTH
if <10ng/mL --> ACTH independent
if 10-20ng/mL --> need CRH testing
if >20ng/mL --> ACTH depdendent
79
What ACTH level suggests ACTH Independent Cushings?
If you confirm ACTH Independent Cushings Syndrome, what is the next test? What are your differentials?
if ACTH <10ng/mL --> ACTH independent
Need CT/MRI adrenals
ddx:
- unilateral mass of adrenal adenoma/carcinoma
- bilateral macronodular or micronodular hyperplasia
80
What ACTH level suggests ACTH Dependent Cushings?
If you confirm ACTH Dependent Cushings Syndrome what is the next test? What are the differentials
if ACTH >20ng/mL --> ACTH depdendent
DDx:
70% Cushings Disease, 10% ectopic, 15% adrenal
Need
1st) MRI pituitary:
- if adenoma <6mm: do BPSS
- if adenoma >6mm AND concordant HDSST then is cushings disease, but if NOT concordant with HDSST then need BPSS
2nd) High dose dexamethasone suppression test (HDSST)
= 2mg dex 6hrly x 8
--> urinary free cortisol suppression >90% is HIGHLY SPECIFIC for Cushings (NOT sensitive)
*** if negative then need BPSS
3rd) Bilateral petrosal sinus sampling (BPSS)
if adenoma <6mm or MRI and HDSST are discordant it is the BEST test
Test before and after CRH
RATIO: inf petrosal ACTH : Peripheral ACTH
--> if >2 then Cushings Syndrome
--> if >=3 then PITUITARY ACTH TUMOUR
** lateralisation within pituitary is possible but less reliable to ddx pituitary versus ectopic
```
4th) if negative BPSS:
THEN do either:
- CT C/A/P
- PET or PET-CT
- Octreoscan
--> if positive then ectopic ACTH tumour
--> if negative then needs followup
```
81
Treatment of Cushings Disease 1st line
Trans-Sphenoidal Selective Resection
--> remission in 80% microadenoma, <50% macroadenoma
RARELY successful if negative MRI
82
Pre-Operative Prep in Treatment of Cushing's Disease
Either:
METYRAPONE:
- inhibits 11beta-hydroxylase activity
- normalises plasma cortisol in 75%
KETOCONAZOLE:
- inhibits several P450 enzymes to lower cortisol
S/E: gynecomastia, LFT, impotence, GI upset and oedema
MIFEPRISTONE:
- glucocorticoid receptor antagonist
- blocks PERIPHERAL cortisol action
- treats HYPERGLYCAEMIA in Cushings
BUT levels of cortisol and ACTH remain high
S/E: hypokalaemia, endometrial hyperplasia, hypoadrenalism, hypertension
83
Role of METYRAPONE in pre-operative management in surgical treatment of Cushings Disease
METYRAPONE:
- inhibits 11beta-hydroxylase activity
- normalises plasma cortisol in 75%
84
Role of KETOCONAZOLE in pre-operative management in surgical treatment of Cushings Disease
KETOCONAZOLE:
- inhibits several P450 enzymes to lower cortisol
S/E: gynecomastia, LFT, impotence, GI upset and oedema
85
Role of MIFEPRISTONE in pre-operative management in surgical treatment of Cushings Disease
MIFEPRISTONE:
- glucocorticoid receptor antagonist
- blocks PERIPHERAL cortisol action
- treats HYPERGLYCAEMIA in Cushings
BUT levels of cortisol and ACTH remain high
S/E: hypokalaemia, endometrial hyperplasia, hypoadrenalism, hypertension
86
If surgery is unsuccessful in treatment of Cushings Disease
1) total hypophysectomy
2) pituitary irradiation (cures in 15%)
3) PASIREOTIDE
4) bilateral adrenalectomy
87
What is the role of Pasireotide in treating Cushings Disease for which surgery has been unsuccessful? What are the side effects?
Pasireotide = somatostatin analogue with high affinity for SST5 >SST2 receptors
- used for treating ACTH-secreting tumours
- in 25% lowers ACTH levels and normalises 24 hour UFC
```
S/E:
- hyperglycaemia and diabetes (75%)
(due to suppressed pancreatic secretion of insulin and incretins)
- GI discomfort
- gallstones (20%)
```
88
What is the consequence of bilateral adrenalectomy in treating Cushings Disease for which surgery has been unsuccessful?
Requires permanent mineralocorticoid and glucocorticoid
If residual corticotrope adenoma can develop NELSON'S SYNDROME
89
What is Nelson's Syndrome and how can it be prevented?
Nelson's Syndrome develops when there is residual corticotrope adenoma after bilateral adrenalectomy for Cushing's DIsease.
- rapid pituitary tumour enlargement
- hyperpigmentation secondary to high ACTH
Can be prevented with prophylactic radiotherapy post adrenalectomy
90
What medical followup is needed post hypophysectomy in treatment of Cushing's Disease?
8AM cortisol: 24 hours post last hydrocortisol and 3-7 days postop
CURE = undetectable cortisol
and undetectable ACTH
91
What is the size definition of a macroadneoma?
>1cm
92
Clinical features of sellar masses?
- headaches
- vision:
Bitemporal hemianopia (ventral optic chiasm)
Homonymous hemianopia (opstchiasmal compression)
Monocular temporal loss (prechiasmal compression)
Diplopia from ocular motor nerve palsy (cavernous sinus)
- symptoms of hypersecretion
- cranial nerve III, IV, VI palsies from impinged cavernous sinus
93
Screening for functional pituitary adenoma?
Acromegaly:
- serum IGF-1
- Oral GTT (normal patient will suppress GH)
Prolactinoma: serum prolactin
Cushings:
- 24hr UFC
- 1mg dex suppression test
- ACTH assay
94
Treatment of hypothalamic/pituitary sellar masses
SURGERY
- trans-sphenoidal preferred
- surgery decompression / resection
S/E: operative mortality 1%
- 20% transient diabetes insipidus / hypopituitarism
- 10% permanent diabetes insipidus / cranial nerve damage / nasal perforation / visual disturbance
- 4% CSF leaK
RADIATION:
- slow onset of action (reserved for post surgical treatment)
- used as adjuvant to surgery
95
Hypothalamic Lesions: features of an anterior/pre-optic region mass
Paradoxical vasoconstriction
Tachycardia
Hyperthermia
96
Hypothalamic Lesions: features of a posterior region mass
Thermo-dysregulation
- "periodic hypothermia syndrome"
= episodes of temps <30, sweating, vasodilation, vomiting and bradycardia
97
Hypothalamic Lesions: features of a ventromedial nucleus lesion
Hyperphagia
| Obesity
98
Hypothalamic Lesions: features of a preoptic nucleus lesion
Polydipsia
| Hypodipsia
99
Hypothalamic Lesions: features of a central region lesion
stimulation of sympathetic system with increased catecholamines and increased cortisol
100
How do craniopharyngiomas present?
```
Usually present <20yrs old
Headaches
Visual field defects
Hypopituitarism (90%)
Diabetes insipidus (10%)
Calcified appearance on MRI
```
101
What are Ranthke's Cysts?
Found in 20% of people from developmental failure of Rathke's pouch obliteration
80% present in adulthood with compression symptoms, hyperprolactinaemia and diabetes insipidus
102
What is Hand-Schuller-Christian Disease?
Diabetes insipidus
Exophthalmos
Punched out lytic bone lesions
Assoc granulomatous lesions on MRI
103
Hypothalamic hamartomas overexpress which hypothalamic neuropeptides?
GnRH
GHRH
CRH
104
Hypothalamic hamartomas are associated with which genetic syndrome?
Pallister Hall Syndrome
(from mutation in GLIS)
Assoc. with:
- imperforate anus
- cardiac / renal / lung disorders
- pituitary failure
105
Where in the pituitary do systemic metastases go?
Posterior pituitary
106
Where do the majority of pituitary metastases originate from?
50% of pituitary metastases are from breast cancer
107
What are the types of pituitary adenoma?
40% are non-functional
- most stain for FSH
- can cause mass effect
- can cause VERY HIGH prolactin due to stalk pressure
- 30% recur post surgery
30% prolactinoma (lactotroph)
15% GH (somatotroph)
10% ACTH (corticotroph)
<5% are TSH (thyrotrope) or FSH (gonadotrope)
108
How many pituitary adenomas recur post surgery?
30%
109
What gene and what features are part of MEN1?
= tumour suppressor gene on Ch11q13
Autosomal dominant
Parathyroid
Pancreatic
Pituitary
110
What gene and what features are part of MEN4
= gene CDKNIB on Ch12p13
Parathyroid
Pituitary
111
What is Carney Complex?
= mutation of R1alpha regulatory subunit of Protein Kinase A (PPKAR1A)
Features:
- atrial myxoma
- spotty skin pigmentation
- endocrine tumour: testicular, adrenal and pituitary
- acromegaly (20%)
112
What is McCune-Albright Syndrome?
= inactivation of GTPase activity of GSalpha
Features:
- polyostotic fibrous dysplasia
- pigmented skin patches
- acromegaly
- adrenal adenoma
113
What is Familial Acromegaly?
= germline mutation in AIP
Generally young onset
Acromegaly and gigantism
114
FSH secretion is stimulated by what?
Gonadotropin Releasing Hormone (GnRH) at low frequency pulses
115
FSH secretion is inhibited by?
Inhibin
- inhibits FSH but NOT GnRH
- produced by females by ovarian granulosa cells in response to FSH
- produced in males by Sertoli cells in response to androgens
116
Mechanism of action of FSH
Stimulates germ cell maturation
FEMALES: initiates follicular selection and growth
MALES: initiates meiosis of primary spermatocytes and enhances ANDROGEN BINDING PROTEIN production from Sertoli cells
117
LH secretion is stimulated by?
Stimulated by gonadotropin releasing hormone (GnRH) at HIGH frequency pulses
118
LH mechanism of action?
FEMALES: "LH surge" triggers ovulation and converts residual follicule into corpus luteum to release progesterone and prepare endometrium for implantation
MALES: acts on testicular Leydig cells to produce testosterone
119
TSH is produced where and in response to what?
Produced in anterior pituitary by thyrotropes in response to TRH
120
TSH secretion is inhibited by what?
```
Growth Hormone Inhibiting Hormone (GHIH)
(aka Somatostatin)
and
Thyroid Hormone
and
Dopamine
```
121
Action of TSH?
Stimulates synthesis and secretion of thyroid hormones by binding to TSH receptor on thyroid follicular cells
122
How do TSH-omas present?
Present with goitre and hyperthyroidism
Suggested by pituitary mass and beta-subunit elevated levels
Need to EXCLUDE resistance to thyroid hormone (= dominant negative thyroid receptor mutation)
123
Developmental causes of Hypopituitarism
- Pituitary dysplasia
- Tissue specific factor mutations
- Kallman syndrome
- Bardet-Beidl Syndrome
- Leptin and Leptin Receptor mutations
- Prader Willi Syndrome
124
What are the tissue specific factor mutations that cause developmental hypopituitarism?
PIT-1 and PROP1 needed for lineages:
TPIT: deficiency of ACTH
PROP1: deficiency of GH, PRL, TSH, Gonadotropin
125
What are the features of Kallman Syndrome?
= defective hypothalamic GnRH (both Autosomal Recessive and Dominant)
Features:
- Anosmia
- Colour Blindness
- Optic atrophy
- Sensorineural deafness
- Cleft palate
- Renal abnormalities
- Cryptorchism
- Neuro: mirror movements
126
What are the features of Bardet-Biedl Syndrome?
- mental retardation
- obesity
- renal abnormalities
- syndactyly
- central diabetes insipidus
- childhood retinal degeneration
127
What are the features of Leptin and Leptin Receptor Mutations?
Hyperphagia
Obesity
Central hypogonadism
128
What are the features of Prader Willi Syndrome?
= deletion of paternal SNRPN and NECDIN on Ch15
Features
- hypogonadotropic hypogonadism
- hyperphagia / obesity
- chronic muscle hypotonia
- mental retardation
- diabetes mellitus
129
Acquired Causes of Hypopituitarism?
Infiltrative Disorders
- Sarcoidosis
- Histiocytosis X
- Amyloidosis
- Haemochromatosis
Inflammatory Disorders
- TB
- opportunistic fungal infections
- tertiary syphilis
Cranial irradiation
- usually after 5 - 15 years
GH deficiency most commonly
Lymphocytic Hypophysitis
Pituitary Apoplexy
Empty Sella
130
What are the features of Lymphocytic Hypophysitis?
- especially postpartum women
- presents with hyperprolactinaemia
- ESR elevated
- Rx: several months of glucocorticoids
131
What are the features and associated conditions of Pituitary Apoplexy?
- pituitary adenoma haemorrhage
- Sheehan's syndrome postpartum
Assoc. conditions:
- Sickle Cell
- Diabetes
- Hypertension
Features:
- Sudden onset headache
- vomiting and neck stiffness
- visual fields: bitemporal superior quadrant defect
- extraocular nerve palsies
- features of pituitary insufficiency
132
What are the features of ACTH deficiency? How is it diagnosed?
Fatigue, n+v and hypoglycaemia
NOT hyperpigmentation or mineralocorticoid deficiency
```
Diagnosis:
- insulin tolerance test (cortisol SHOULD increase if glucose decreases)
- CRH test
- basal cortisol
SYNACTHEN TEST: increases cortisol
```
133
How to diagnose TSH deficiency
Basal test TFTs
| TRH stimulation test --> should increase TSH
134
How does deficiency of FSH and LH present? How do you diagnose?
Presents as amenorrhoea, infertility and reduced libido
Diagnose:
- basal tests: LH, FSH, testosterone and oestrogen (low levels indicate insufficiency)
- GnRH test: should normally increase FSH and LH
135
Where is Vasopressin (AVP / ADH) produced
Encoded on Ch20 then packaged and transported down neurohypophysis axon to posterior pituitary and is then processed to ADH, neurophysin and copeptin
136
What stimulates vasopressin secretion?
Increased osmolality
| Angiotensin II
137
What inhibits vasopressin secretion?
ANP
Alcohol
Cortisol
138
What is the mechanism of vasopressin?
Acts on receptors:
Vasopressin 1A Receptor:
- in liver, kidney, brain and peripheral vascular
- vasoconstriction
- platelet aggregation
- gluconeogenesis
Vasopressin 2 Receptor:
- on basolateral membrane in cortical collecting duct
- stimulates insertion of AQP2 channel
139
Where is Vasopressin 1A Receptor found and what does it do?
Found in liver, kidney, brain and peripheral vascular
- vasoconstriction
- platelet aggregation
- gluconeogenesis
140
Where is Vasopressin 2 Receptor found and what does it do?
Found on basolateral membrane in cortical collecting duct
Stimulates insertion of AQP2 channel
141
Where is oxytocin synthesised?
In paraventricular nucleus of the hypothalamus
142
What stimulates secretion of oxytocin?
- uterus or cervical distention
- nipple stimulation
- oestrogen
143
What is the action of oxytocin?
Milk ejection
| Uterine contractions
144
What is the most common genetic inheritance of pituitary diabetes insipidus?
Most common form is autosomal dominant (some are autosomal recessive)
145
What is Wolfram's Syndrome?
also known as DIDMOAD
= Autosomal recessive mutation in WFS1
Diabetes Insipidus
Diabetes Mellitus
Optic Atrophy
Deafness
146
What is the effect of primary polydipsia on ADH?
Primary polydipsia excessive fluid intake inhibits ADH secretion
147
What is the most common genetic form of nephrogenic diabetes insipidus?
Most common is semirecessive X-linked
148
What medications can cause nephrogenic diabetes insipidus?
Lithium
Aminoglycosides
Cisplatin
149
What are the causes of nephrogenic diabetes insipidus?
Genetic
Medications (lithium / aminoglycosides / cisplatin)
Obstructive
Granulomas (ie sarcoidosis)
Infiltrative (ie amyloidosis)
Metabolic (ie hypercalcaemia / hypokalaemia)
150
How is diabetes insipidus diagnosed?
Water deprivation:
- FAILS to concentrate urine Osm >600 despite a raised serum Osm >300
Then CONFIRM CENTRAL iwth desmopressin ddAVP --> central if urine Osm >600
151
Treatment of central diabetes insipidus?
If temporary/mild: ensure access to fluid
If severe/permanent: desmopressin nasal spray or tablets
152
What percentage of patients with acromegaly have a MEN syndrome? Which one is it?
6% have MEN-1
153
What are the primary and secondary causes of hypoadrenalism?
PRIMARY:
- TB
- metastases (ie bronchial carcinoma)
- meningococcal septicaemia (Waterhouse-Friderchsen syndrome
- HIV
- antiphospholipid syndrome
SECONDARY
- pituitary disorders
- exogenous glucocorticoids
154
Causes of gynaecomastia?
physiological: normal in
puberty
syndromes with androgen deficiency:
- Kallman's
- Klinefelter's
testicular failure:
- mumps
liver disease
testicular cancer
- seminoma secreting hCG
ectopic tumour secretion
hyperthyroidism
haemodialysis
drugs
155
Common drug causes of gynaecomastia?
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
gonadorelin analogues
- Goserelin
- buserelin
oestrogens
anabolic steroids
156
Very rare drug causes of gynaecomastia?
tricyclics
isoniazid
calcium channel blockers
heroin
busulfan
methyldopa
