Hyperprolactinemia and Hyperaldosteronism Flashcards
1
Q
Hyperprolactinemia
-epidemiology
A
-condition of elevated serum prolactin
- women are more likely to be diagnosed than men
- women aged 25-34 years
2
Q
Hyperprolactinemia
-pathogenesis (6)
A
- prolactin is produced and secreted by anterior pituitary, inhibited by dopamine
- prolactin is metabolized by the liver and the kidney
- if dopamine delivery is impaired –> prolactin secretion increases and hyperprolactinemia develops
- it may develop as a result of physiological, pharmacological or pathological effect on the hypo-pituitary dopaminergic connections
- in women –> prolactin inhibits ovulation by blocking GnRH production and secretion –> infertility
- in men –> elevated prolactin –> GnRH inhibition –> inhibition of spermatogenesis –> infertility
3
Q
- Primary function of prolactin
2. Consequences of prolonged hyperprolactinemia
A
- stimulate milk production in response to lactation
2. secondary reduction in bone mineral density
4
Q
Prolactin synthesis and secretion are affected by:
- Prolactin releasing factors
- Prolactin inhibiting factor
A
- Thyrotropin releasing hormone (TRH), Vasoactive intestinal peptide (VIP), endothelial growth factors, dopamine antagonists, estrogen
- Dopamine
5
Q
Hyperprolactinemia
-etiology (6)
A
- physiological –> coitus, exercise, lactation, pregnancy, sleep, stress
- pathological –> pituitary or hypothalamic-pituitary stalk damage
- systemic disorders –> chronic renal failure, cirrhosis, PCOS, hypothyroidism
- pharmacological
- genetic mutations (MEN1)
- ectopic production
6
Q
Hyperprolactinemia
- signs and symptoms:
1. women (6)
2. men (6)
A
- galactorrhea, oligomenorrhea, amenorrhea, decreased libido, infertility, low bone mass (osteoporosis, osteopenia)
- gynecomastia, galactorrhea (rare), decreased libido, infertility, erectile dysfunction, low bone mass (osteoporosis, osteopenia)
7
Q
Hyperprolactinemia
-diagnostics
A
If serum prolactin is elevated:
- exclude physiological and pharmacological causes
- neuroradiological imaging of hypothalamic-pituitary region
Lab test
- serum prolactin and macroprolactin
- breast examination
* **it is necessary to determine serum prolactin 2 times or more because its secretion is pulsatile
8
Q
- Macroprolactin (4)
2. Normal prolactin ranges
A
- present in asymptomatic hyperprolactinemia
- represents large circulating aggregates of prolactin and antibodies –> they are biologically inactive –> can be misdiagnosed as prolactin hypersecretion
- PEG >65 % - true hyperprolactinemia
- PEG <30 % macroprolactinemia
- Women 72-511 (3-25 ng/mL)
- Men 86-390 (2,2-20 ng/mL)
9
Q
Hyperprolactinemia
-treatment
A
- dopamine agonists (DA) –> reduce prolactin hypersecretion and clinical symptoms
- if asymptomatic –> treatment is not recommended
- drugs –> most common cause of non-tumor hyperprolactinemia
- DA - Bromocriptine and Cabergoline
- Cabergoline is preferred –> higher efficacy, fewer side effects
- not prescribed during pregnancy
10
Q
Hyperprolactinemia
- duration of treatment
- withdrawal of medication
A
- after start of treatment –> PRL test i repeated every 1 month and later every 1-2 months
- normoprolactinemia not achieved –> gradually increase dose
- normoprolactinemia is achieved –> dose adjustment –> after 2 years, it may be discontinued
- investigate prolactin level 3 days after stopping it
- if it rises >50% –> restart treatment
11
Q
Prolactinoma (4)
A
- most common cause of PRL excess
- benign tumor of lactrophs
- micro <10mm diameter
- macro >10mm diameter
12
Q
Prolactinoma
-pathogenesis
A
-tumors inhibit dopamine induced hyperprolactinemia because of pressure on the pituitary stalk or interruption of the vascular connections between the pituitary and hypothalamus
13
Q
Prolactinoma
-epidemiology (5)
A
- more common in women
- microadenomas are more common
- macroadenomas are more common in men
- clinical presentation in women are more obvious and present earlier than in men
- may be associated with MEN1 syndrome
14
Q
Prolactinoma
- Sign and symptoms caused by high prolactin
- Sign and symptoms caused by mass effect
- Local effects
A
- women: oligomenorrhea, amenorrhea, infertility, galactorrhea, low bone mass
men: decreased libido, impotence, infertility, oligospermia, gynecomastia, erectile dysfunction, low bone mass - headache, visual field defect, external ophthalmoplegic, bitemporal hemianopia
- chiasmatic compression, cranial nerve damage, hypothalamic damage, bony invasion: pain, CSF leaks
15
Q
Prolactinoma
-diagnosis (6)
A
- when PRL is elevated 10-fold above normal
- macroprolactinoma 200 and above
- macroprolactin and serum prolactin
- MRI of the pituitary with contrast
- visual field testing
- no possible markers for predicting the possible malignancy of prolactinoma
16
Q
The Hook effect (2)
A
- sometimes, patients can have clear symptoms of hyperprolactemia but lab results are negative because of increased concentration of the hormone.
- so a dilution method is used to get a clear result.
17
Q
Prolactinoma
-treatment (5)
A
- medical: dopamine agonist
- surgical: transsphenoidal surgery
- radiation treatment
- surgery and radiation is only done when patient is resistant to medical treatment
- microprolactinoma - dopamine agonists for 2 years
18
Q
Transsphenoidal surgery
- indications (4)
- complications (3)
A
- the patient is intolerant to high doses of DA
- resistance to DA
- macroprolactinoma with threat of optic nerve damage
- suspected malignancy
-hypopituitarism, diabetes insipidus, cerebrospinal fluid leaks
19
Q
Radiation therapy
- indications (3)
- complications (4)
A
- relapse after surgical treatment, aggressive prolactinoma, malignant prolactinoma
- hypopituitarism, damage to cranial nerves, increased stroke probability, secondary tumor formation
20
Q
Adrenal gland
-parts
A
- outer –> adrenal cortex
- inner –> medulla
the cortex has 3 layers (zones)
- Zona glomerulosa (mineralocorticoids)
- Zona fasciculata (glucocorticoids)
- Zona reticularis (androgens)
21
Q
Primary hyperaldosteronism
- definition
- characterized by: (5)
A
- renin-independent aldosterone hyperproduction syndrome
- increased aldosterone secretion, decreased plasma renin activity (PRA), increased arterial BP, hypokalemia and metabolic alkalosis
22
Q
Primary hyperaldosteronism
- most common cause of:
- Conn’s syndrome
A
- secondary hypertension
- patients have a higher incidence of cardiovascular disease
-primary hyperaldosteronism because of aldosterone producing adenoma
23
Q
Primary hyperaldosteronism
-hypersecretion of aldosterone causes: (5)
A
- hypertension
- affects the cardiovascular system
- suppress plasma renin activity (PRA)
- decreases sodium excretion in the kidneys
- increases potassium excretion –> hypokalemia
24
Q
Renin-angiotensin-aldosterone system
A
- regulates sodium circulation and BP
- raises sodium and water reabsorption and increases vasoconstriction
- main components –> renin, angiotensin II, aldosterone
- Renin
- Angiotensinogen –> angiotensin I
- Angiotensin I + angiotensin converting enzyme (ACE)
- Angiotensin II –> stimulates adrenal glands
- Aldosterone
25
Q
Factors that stimulate renin secretion (3)
A
- decreased arterial BP
- decrease sodium concentration
- sympathetic nervous system activity (beta 1)
26
Q
- Angiotensin II - what does it do (7)
2. Aldosterone - what does it do
A
- increases BP, reduced renal blood flow, increases aldosterone secretion, enhances the release of norepinephrine and epinephrine, stimulates center of thirst in hypothalamus, increase osmotic pressure, release ADH
- sodium and water reabsorption and potassium secretion –> increase BP, decrease potassium
27
Q
Types of Primary hyperaldosteronism (6)
A
- aldosterone producing adenoma
- bilateral idiopathic hyperaldosteronism or idiopathic hyperplasia
- unilateral hyperplasia or primary adrenal hyperplasia
- pure aldosterone-producing adrenocortical carcinoma
- familial hyperaldosteronism
- ectopic aldosterone secreting tumors
28
Q
Primary hyperaldosteronism
-clinical presentation (4)
A
- arterial hypertension (severe >150/>100 mmHg)
- hypokalemia - muscle weakness and cramping
- mild hypernatremia
- metabolic alkalosis - due to hypokalemia and aldosterone H+ urinary excretion
29
Q
Primary hyperaldosteronism
-lab tests - diagnosis (4)
A
- measure plasma renin activity (PRA) or plasma renin concentration (PRC) and plasma aldosterone concentration (PAC)
- increased PAC/PRA ratio –> suspicious for primary aldosteronism –> screening test
- oral sodium loading test - high sodium diet for 3 days –> urine test –> measure aldosterone, sodium and creatinine
- intravenous saline infusion test - after an overnight fast –> values above 10 ng/dL (277 pmol/L) are conclusive
- Captopril challenge test
30
Q
Primary hyperaldosteronism
-imaging tests - diagnosis (2)
A
- Adrenal computed tomography (CT) - adrenal carcinoma should be suspected when a unilateral, large (>4cm) adrenal mass is found on CT
- Adrenal vein sampling (AVS) - before planning surgical management –> invasive, often unsuccessful
31
Q
Primary hyperaldosteronism
-treatment
A
- surgery –> for patients with unilateral disease
- medication –> for patient with bilateral adrenal hyperplasia
- FH type I –> glucocorticoids
32
Q
Primary hyperaldosteronism
-medications
A
Mineralocorticoid receptor antagonist - potassium sparing diuretics:
- Spironolactone - the most effective, but has antiandrogenic effect (can cause painful male gynecomastia, erectile dysfunction and decrease libido). Contraindicated during pregnancy
- Eplerenone - has no antiandrogenic effect. Can be used during the pregnancy
Antihypertensive therapy
-ACE inhibitors, ARBs, calcium channel blockers
33
Q
TSH and prolactin (2)
A
- Primary hypothyroidism causes an elevation of TRH, which can cause an elevation of prolactin along with TSH.
- Prolactin levels in patients with hypothyroidism tend to be lower than those usually seen with prolactinomas (the latter are usually 150-200 ng/mL or higher).
34
Q
Primary vs Secondary hyperaldosteronism
A
- Primary - high aldosterone, low renin
2. Secondary - high aldosterone, high renin
35
Q
Diagnostic steps for the diagnosis of hyperaldosteronism (6)
A
- typical symptoms
- aldosterone to renin ratio
- if abnormal –> confirmatory tests (oral sodium loading test, IV saline infusion, Captopril challenge test)
- if confirmatory tests are abnormal –> adrenal CT scanning
- if patient is unsuitable for surgery –> medication, if not –> adrenal venous sampling
- unilateral –> laparoscopic ADX, bilateral –> MR antagonists
36
Q
Hyperprolactinemia
-treatment - side effects (7)
A
- nausea
- vomiting
- postural hypotension
- nasal stiffness
- depression
- digital vasospasm
- high doses –> associated with a risk of heart valve regurgitation
37
Q
Who should be tested for primary hyperaldosteronism? (7)
A
- severe hypertension
- drug-resistant hypertension
- hypertension and family history
- all hypertensive first-degree relatives of patients with PH
- hypertension and spontaneous or low dose, diuretic induced hypokalemia
- hypertension with adrenal incidentaloma
- hypertension with sleep apnea
38
Q
Conditions for examining a patient with hyperaldosteronism (4)
A
- potassium levels should be corrected first –> hypokalemia suppresses aldosterone
- 2 weeks prior to testing use sufficient amount of salt (>6g/d)
- Blood is drawn in the morning after the patient has spent 2hour in the vertical position and sat for 15-60minutes before taking blood
- Stop medications which could influence the results
39
Q
When to order macroprolactin values? (2)
A
- asymptomatic or patients with not so expressed symptoms
- older women with hypophysis tumor and we need to assess for normal deficiency
