Endocrine Flashcards
Which Thyroid function test is tested at first?
TSH first, if TSH abnormal then free T4.
What is Thyrotoxic Periodic Paralysis?
- Asian male
- Presents with sudden generalised paralysis of 4 limbs (sparing bulbar and respiratory muscles) and normal sensory function
- Precipitated by strenuous exercise or heavy carbohydrate-rich meal (since activate Na/K transporter—>hypokalemia)
-Characterized by severe hypokalemia which results from trans cellular shift of potassium from extra to intra cellular compartments
-hypokalemia leads to paralysis, rhabdomyolysis and typical ECG function
-main pathology is increased Na/K ATPase activity due to thyroitoxicosis and associated beta-adrenergic response
Glucose challenge increase insulin secretion —> increase Na/K ATPase activity - Exercise release K from skeletal muscle and resting posting-exercise promote influx of K
Mx of TPP
- Carefullly replace potassium
-> only small doses are needed to normalise potassium level as there is no net loss of body potassium
-> Excessive replacement may cause rebound hyperK
-propranolol
-> beta0blocker inhibits catecholamine-induced Na/K ATPase over activity
-monitor renal function
-monitor ECG
-ICU admission is often required
Differential diagnoses of sellar mass
• Pituitary adenoma (MC)
• Craniopharyngioma (benign tumor
from Rathke’s pouch, often cystic)
• Other tumors: pituitary CA (very
rare), metastatic tumor (esp. breast),
germ cell tumor, lymphoma
• Non-neoplastic mass: Rathke cleft
cyst, arachnoid cyst
Mass effects of pituitary mass
• Headache: stretching of diaphragm sellae / dura
• Visual defect: classically bitemporal hemianopia (optic chiasm), but can also be unilateral visual loss (optic nerve)
or homonymous hemianopia (optic tract)
• Diplopia: lateral extension of sellar mass into cavernous sinus
• Disconnection hyperprolactinaemia: decreased inhibition on prolactin secretion
Types and associations of pituitary of adenoma
• Microadenoma (<1cm) vs macroadenoma (≥1cm)
• Functional vs non-functional
• Associations: MEN1, MEN4, Carney complex, McCune-Albright syndrome
Pituitary microadenoma cause what?
Hormone excess:
- Hyperprolactinaemia
- galactorrhoea
- amenorrhoea
- hypogonadism - Acromegaly
- headache
- sweating
- change in shoe and ring size - Cushing’s disease
- weight gain
- bruising
- myopathy
- hypertension
- striae
- depression
Clinical features of macroadenoma
- Local complications
- headache
- visual filed defect
- disconnection hyperprolactinaemia
- diplopia (cavernous sinus involvement)
- acute infarction/expansion (pituitary apoplexy) - Hypopituitarism
- growth hormone —> lethargy
- gonadotropins —> lethargy, loss of libido, hair loss, amenorrhoea
- ACTH —> lethargy, postural hypotension, pallor, hair loss
- TSH —> lethargy
- vasopressin (ADH) —> thirst and polyuria - hormone excess
- hyperprolactinaemia
- acromegaly
- Cushing’s disease
Ix and Mx of pituitary mass
Investigations:
• Hormonal profile
o Pulsatile secretion (e.g. GH, ACTH): require dynamic testing
o Constant secretion (e.g. PRL, TSH, LH/FSH): can be directly measured (usually 9am)
• Anatomical diagnosis:
o Skull X-ray: double flooring (asymmetrical enlargement)
o MRI pituitary (T1-weighted)
o Visual field testing (perimetry)
Management of pituitary tumour:
• Non-functional microadenoma: observe with serial hormone measurement and MRI scan
• Functional / Macroadenoma / Mass effect +ve:
o Prolactinoma: medical therapy (DA agonist) (1st line) —> surgery / RT
o Others (e.g. acromegaly, Cushing’s disease): surgery (1st line) ± adjunct RT for residual tumor
What is pituitary apoplexy?
• Definition: sudden haemorrhage into pituitary gland
• Clinical features
o Increased ICP: sudden-onset excruciating headache, n/v, altered mental state, neck rigidity and photophobia
o Compression on optic pathway: visual field defect
o Involve Cavernous sinus: diplopia (CN3/4/6)
o Other neurological manifestation: extravasation of blood into SAH —> meningism
o Hypopituitarism: severe hypoNa (due to adrenal crisis/SIADH/hypothyroidism)
• Investigations
o CT/MRI pituitary for definitive diagnosis
• Management: Surgical decompression + steroid cover
o Indicated if signs of increase ICP, decrease GCS, or evidence of compression onto surrounding structures
Etiology and clinical features of Hypopituitarism
Etiology:
- tumour : Non-functioning adenoma (MC)(mass effect), craniopharyngioma (stalk effect)
- iatrogenic: hypophysectomy, post-RT
- infarction: pituitary apoplexy, Sheehan’s syndrome
- others: TB infection, empty sellar syndrome
Clinical features:
- mass effect
- hormone deficiency: usually in the order of GH> LH/FSH>ACTH>TSH
o Acute insult may cause Addisonian crisis
Ix of Hypopituitarism
• MRI pituitary & formal visual field testing
• Hormonal function assay
Adrenal —> ACTH/ LDSST —> Clinical monitor
Thyroid —> fT4/ TSH —> fT4 monitor
Gonad —> LH/FSH/E2/T —> Testosterone (measure mid-way between injection)
• Management
o Hydrocortisone 20mg/day
- Avoid nocte (risk of insomnia)
- Stress dose: double dose (risk of Addisonian crisis) be aware of DI unmasking since hydrocortisone destroy ADH
o Thyroxine 1.6mcg/kg/day
- Start AFTER hydrocortisone is given (risk of Addisonian crisis) Thyroxine destroys cortisol
o DDAVP sublingual
o Sex hormone: depend on gender & fertility wish
1. No fertility wish
-Male:
—> Testosterone (more physiological): IM Sustanon Q4 weeks (S/E: BPH, dLFT, polycythemia)
-Female:
Combined oral contraceptive pills (E+P)
- Fertility wish
-Male:
—> Gonadotropins/ GnRH (testosterone does not restore spermatogenesis)
-Female:
—> Gonadotropins/ GnRH
Etiology and clinical features of hyperprolactinaemia
Aetiology (SAQ!)
• Hypothalamic/ pituitary: pituitary tumour (non-functioning, prolactin-secreting, prolactin & GH-secreting),
pituitary stalk damage (e.g. RT, trauma, tumors)
• Drug-induced: DA antagonist (e.g. metoclopramide, domperidone*), DA-depleting drugs (e.g. methyldopa)
• Systemic disorders: primary hypothyroidism (TRH), CKD, liver cirrhosis
• Physiological: pregnancy / lactation, stress, chest wall stimulation (e.g. herpes zoster)
*Domperidone in hyperprolactinaemia
• Domperidone does not cause EPSE:
not cross BBB (c.f. metoclopramide)
• Domperidone causes hyperPRL:
pituitary has no BBB
Clinical features
• Mass effect
• Galactorrhoea (F) / Gynaecomastia (M)
• Hypogonadotrophic hypogonadism:
o Male: decrease libido, decrease shaving frequency, erectile dysfunction, infertility
o Female: amenorrhoea, infertility, climacteric symptoms, decrease BMD
• Concomitant acromegaly (GH as common lineage)
Presentations varies with gender & pathology
• Pathology: prolactinoma presents earlier, non-
functioning pituitary adenoma presents late
(mass effect: macroadenoma ≥ 1cm)
• Gender: female presents earlier (amenorrhoea),
male presents late
Ix of hyperprolactinaemia
• Pregnancy test
• Prolactin level: PWH assay automatically ruled out macroPRL
o <500 = normal
o >1000: consider prolactinoma
o >5000: highly suggestive of macroprolactinoma
o >100,000: high-dose hook effect (false negative)
• Underlying cause:
o MRI pituitary: indicated if symptomatic / PRL > 1000 / evidence of pituitary insufficiency (e.g. hypoT4)
o RFT, LFT, TFT
• Screen other endocrine axes: IGF-1, ACTH/ cortisol, TSH/ T4, LH/ FSH/ E2/ T
Mx of hyperprolactinaemia
• Dopamine agonist (e.g. bromocriptine, cabergoline) – 1st line (decrease PRL secretion + decrease size of prolactinoma)
o Aim: to avoid long-term consequence of hypogonadism
o Indications:
- Symptomatic (regardless of serum prolactin)
- Serum prolactin >10,000
- MRI pituitary macroadenoma
- MRI pituitary microadenoma + hyperPRL
o Drug choice: cabergoline has higher efficacy, less S/E, less frequent dosing; bromocriptine in pregnancy
o Duration:
- Taper off after 2 years of normal PRL levels (for microadenoma only)
- Otherwise keep until menopause
o S/E: n/v, postural hypotension, constipation, psychosis, retroperitoneal fibrosis, cardiac valve fibrosis (TR)
o Advise contraception prn (fertility might return after PRL normalizes)
• Transsphenoidal surgery (TSS) ± adjuvant RT - 2nd line
o Indications:
- Remain symptomatic/ high PRL despite medical treatment
- DA agonist fails to shrink the tumour significantly (macroadenoma)
- Pituitary apoplexy
- Planning pregnancy
o Adjuvant RT (EBRT / stereotactic radiosurgery): if residual mass after resection and histology shows
radiosensitive tumour
o Complications & management:
- Hypopituitarism: high dose IV hydrocortisone since the day of surgery
- DI —> SIADH —> DI: monitor I/O, Na, urine osmolality daily
- CSF rhinorrhoea: test fluid for beta transferrin
- Diplopia: damage to optic chiasm
• Issues in pregnancy:
o Considering conception: bromocriptine is preferred (∵shorter-acting than cabergoline)
o Consider transsphenoidal surgery before conception
o If pregnant:
- Stop bromocriptine once pregnancy is confirmed
- Monitor visual field and MRI if symptomatic —> may need to restart bromocriptine
- Stop bromocriptine after delivery (C/I in breastfeeding)
