Thyroid Flashcards
Increased uptake RAI
- Hyperthyroidism due to Graves, multinodular goiter or thyroid adenoma
- Goitre
- Early-stage of Hashimoto thyroiditis
- Iodine deficiency
- TSH-producing adenoma
- The recovery phase from subacute, silent, or postpartum thyroiditis
- Pregnancy
- Lithium carbonate therapy
- Withdrawal of antithyroid medication
- Rebound after the suppression of thyrotropin
- Congenital defects of thyroid hormone synthesis
- Thyroid cancer (papillary or follicular)
- Trophoblastic disease
- TH resistance
Decreased uptake RAI
- Primary hypothyroidism (for example in congenital hypothyroidism)
- Central hypothyroidism
- Destructive thyroiditis
–Subacute thyroiditis
–Silent thyroiditis
–Postpartum thyroiditis
–Palpation thyroiditis
-Excess iodine
-Dietary supplements
-Radiological contrast
-Medications
–Amiodarone
–Antithyroid drugs
–Perchlorate
–Thiocyanate
–Sulphonamides
–Sulphonylurea
–High-dose glucocorticosteroids
–Topical iodine
-Post-thyroidectomy
-External neck radiation
-Thyroid cancer (nodule more likely to be malignant if “cold” nodule) - Struma Ovarriii
Teratogenic effects of MMI
- cutis aplasia (classic)
- choanal aresia
- esophageal atresia
- omphalocele
- VSD
Reasons for false negative CH NBS
- Central hypothyroidism
- Prematurity (may have delayed TSH increase)
- Low birth weight
- Monozygotic twin (mixing of fetal blood)
- Dopamine therapy (rapidly decreases TSH release)
- Acute Illness
false positive CH NBS
Blood sample is drawn too early, prior to 24hrs of life
1 cause of hypothyroidism worldwide
iodide deficiency
most common thyroid dyshormonogenesis cause
organification defect
Hemangiomas effect on thyroid?
consumptive hypoT
type 3 deiodinase
can be severe hypo
hemangioma could be not visible - ex liver
Pendred syndrome
PDS gene
SLC26A4 gene
defect in transport of I to colloid
presentation: goitre, later childhood
10% have SNHL
causes of poor neurodevelopmental outcomes that are associated with CH
- Late diagnosis
- Late initiation of treatment
- Undertreatment
- Overtreatment
- Prolonged time taken to normalize of thyroid function (TSH)
- Poor attendance of clinic visits
Poor control during first year of life
Associated markers for poor neurodevelopmental outcomes, CH severity:
○ Initial T4
○ Initial TSH
○ Bone immaturity
§ Ie: absent knee epiphyses at term
○ Etiology (ie: thyroid agenesis)
○ Parental education
○ Rural setting
○ Access to NBS program
goal for tx of CH
TSH - upper half of the reference range during the first 3 years of treatment
characteristic of hasimoto
- Characterized by lymphocytic infiltration of the thyroid gland, which results in thyromegaly
neonatal signs of hypothyroidism
○ macroglossia
○ umbilical hernia
○ large anterior fontanelle with wide sutures
○ jaundice
○ cool to touch
○ hypotonia
○ delayed reflexes
Drugs that interfere w thyroid function - need to increase Synthroid
Inhibition of levothyroxine absorption (will need more!)
○ Iron
○ Calcium
○ Soy
○ PPI
○ Aluminum hydroxide
○ Colestyramine
○ Colestipol
○ Sucralfate
○ Raloxifene
Increased hepatic metabolism (will need more!)
○ Phenobarbitol
○ Phenytoin
○ Carbamazepine
○ Rifampin
○ TKI (Imatinib, axitinib, motesanib, vandetanib)
Rexinoids
Increased thyroxine binding globulin levels (will need more - more T4 bound to TBG so less is free)
○ Estrogen
○ Raloxifene
○ Tamoxifen
○ Methadone
○ Mitotane
Fluorouracil
Drugs that interfere w thyroid function - need to decrease Synthroid
Decrease hepatic metabolism (will need less!)
○ Metformin (not great evidence)
Inhibition of 5’ deiodinase
○ Propylthiouracil
○ Methimazole
○ Propranolol
○ Glucocorticoids
○ Iodide
Decreased thyroxine binding globulin levels (will need less!)
* Androgens
* Glucocorticoids
* Nicotinic acid
effect of amiodarone on TFT
- inhibiting TH entry into peripheral tissues
- inhibiting type I 5’-deiodinase activity which converts T4 to T3 and reverses T3 to T2. (This inhibition may continue months after amiodarone withdrawal.)
- inhibiting type II 5’-deiodinase which converts T4 to T3 in the pituitary
- failure to escape from the Wolff-Chaikoff effect
- precipitating or exacerbating preexisting organ-specific autoimmunity in susceptible individuals, such as those with autoimmune thyroiditis
dysregulating thyroid hormone synthesis, especially in patients with thyroid nodules or goiter.
effector lithium on thyroid function
- inhibits TH synthesis and secretion
- usually hypothyroid
- increased AITD
v rarely hyperthyroid
Cystinosis
- what is it
-features
Lysosomal storage dz
Photophobia
Renal problems
Hypothyroidism
Labs in hypoT
- Hypercholesterolemia (↑ LDL)
- Hyponatremia (increased total body water)
- Anemia (↓ erythropoietin, ↓ oxygen requirement)
- Elevated creatinine kinase and LDH (from skeletal muscle)
- Reduced GFR
- Elevated liver transaminases
Exam hypoT
- Reduced heart rate and decreased cardiac contractility
- Delayed relaxation phase of DTRs
- Dry skin (↓ sweat and sebaceous gland activity)
- Periorbital puffiness, non-pitting edema (hyaluronic acid)
Myxedema - exam
-Altered mentation
-Alopecia
-Bladder dystonia and distension
-Cardiovascular
–Elevated diastolic blood pressure—early
–Hypotension—late
–Bradycardia
-Delayed reflex relaxation
-Dry, cool, doughy skin
-Gastrointestinal
–Decreased motility
–Abdominal distension
–Paralytic ileus
–Fecal impaction
–Myxedema megacolon—late
-Hypoventilation
-Hypothermia
-Myxedematous face
–Generalized swelling
–Macroglossia
–Ptosis
–Periorbital edema
–Coarse, sparse hair
-Non-pitting edema
Myxedema labs
-Anemia
-Leukopenia
-Elevated CK
-Elevated creatinine
-Elevated transaminases
-Respiratory
-Hypercapnia
-Hypoxia
-Respiratory acidosis
-Hyperlipidemia
-Lytes & glucose:
–Hypoglycemia
–Hyponatremia
tx myxoedema coma
- ICU
- ABCDE
- Levothyroxine
- Steroids (until AI can be rules out)
=/- Abx if concern infection
why does TSH def happen AFTER starting GH tx?
Thought to be due to increased somatostatin secretion in response to pulsed doses of GH
Endo abnormalities in acquired hypoT
- Elevated prolactin
○ Due to TRH stimulation from the hypothalamus - Delayed puberty / irregular periods
○ Altered and blunted LH pulsatility
○ Elevated prolactin - Pseudoprecocious puberty (van Wyk-Grumbach syndrome)
- Decreased and impaired spontaneous GH secretion
○ Need TH for GH secretion!!!
(That’s why you need to check TFTs before GH stim!!)
TSHR mutations?
Activating somatic mutations - solitary or multiple hyperfunctioning adenomas
Activating germline mutation – congenital hyperthyroidism (mimics neonatal Graves)
Inactivating mutation - TSH resistance
- with uncompensated or compensated hypothyroidism
TSH resistance
TSHR
GNAS
TSHR: can be complete, mod or mild resistance
GNAS: PHP
TSH secreting adenoma
- pres
- lab
Pres: Mild thyrotoxicosis and goiter
May have other pit def
Lab: high fT4, T3, and normal or high TSH
Molar ratio of TSH α subunit: TSH >5.7 is usually diagnostic of the presence of a TSH-secreting pituitary adenoma
HyperT DDx
- Graves autoimmune hyperthyroidism
- Autonomously functioning (hot) nodule
- Toxic Multinodular goitre
- Hashitoxicosis
- Subacute (viral) thyroiditis
- Acute thyroiditis
- Familial non-autoimmune hyperthyroidism
- McCune-Albright syndrome
- TSH adenoma
- Thyroid hormone ingestion
- Ingestion of ground beef (inclusion of strap muscles)
- Struma ovarii
Mimicer: Thyroid hormone resistance (RTH), TBG d/o
Signs of GO
- Lid lag
- Corneal dryness
- Erythema
- Tearing
- Strabismus
- Vision loss
MMI s/e
- Minor adverse effects in up to 20% of patients
- Major side effects : 1%
- Allergic reaction
- Minor S/E
○ Rash
○ Arthritis
○ Myalgia
○ Neutropenia
○ Hypothroidism
○ Elevated LFTs
○ H/a - Major S/E
○ Hepatic necrosis, cholestatic jaundice
○ Stevens-Johnson syndrome
○ Vasculitis
○ Agranulocytosis
BBlockers for Graves
- Propranolol: non selective
– decreases T4->T3 conversion - Atenolol : cardio- selective
Mgmt GO
-Smoking cessation
-Referral to ophthalmologist
-Symptom relief (topical lubrication, etc)
-Rapid normalization of hyperthyroidism
–Avoid RAI
-Mild disease – head elevated at night, and diuretics to decrease periorbital edema
-Prednisone (after RAI) – 0.4mg/kg/d
–reducing the dose by 10 mg every 2 weeks, protects against exacerbation of ophthalmopathy following RAI
-Severe/acute disease
–High-dose corticosteroids
–Weekly pulse of high dose IV methylpred shown to be more effective and less
–If not effective or recurrence after steroids taper external X-ray therapy to retrobulbar area
-If vision is threatened - orbital decompression
how do MMI/PTU work
1) block TPO
- oxidation, organificaiton, coupling
2) block peripheral conversion (PTU only)
3) Immunosuppressive impact (MMI only)
Prep for surgery for Graves
- achieve euthyroid state (MMI)
- give KI pre op before to decrease thyroid vascularity (decrease bleeding)
reasons for surgery > RAI in graves
- Refuse RAI
- Low uptake RAI
- Symptomatic compression or large goiters
- Severe hyperthyroidism (? unable to make them hypothyroid pre-RAI)
- Very high TSI
- Smoker
- Severe eye disease
- Age <5yo
- Pregnant currently with severe Graves
- Women planning a pregnancy in <6 months provided thyroid hormone levels are normal (i.e., possibly before thyroid hormone levels would be normal if RAI were chosen as therapy)
- Concomitant suspicious or malignant thyroid nodule
- Multinodular goiter
- Large thyroid nodules especially if greater than 4 cm or if nonfunctioning, or hypofunctioning on 123I or 99mTc pertechnetate scanning
- Coexisting hyperparathyroidism
Comp of surgery in Grves
- Hypothyroidism (likely/inevitable)
- Thyroid storm
- Hypoparathyroidism (transient or permanent)
- Recurrent laryngeal nerve injury
- Infection
- Bleeding
- Keloid formation
Anesthetic complications
Mgmt in thyroid storm
- Thianomide (PTU>MMI)
- BBlocker
- Iodine
- Steroids
Neonatal Graves: fetal u/s findings
- fetal goiter
- increased thyroid vascularity
- fetal tachycardia
- heart failure with non-immune hydrops
- IUGR
- preterm birth
- craniosynostosis
- advanced skeletal maturation
Neonatal Graves: neonatal findings
VITALS:
- tachycardia
- hypertension
- hyperthermia
- poor weight gain
EXAM:
- goitre +/- tracheal compression
- SGA
- small AF
- eye findings: Stare, periorbital edema, retraction of the eyelid
- irritability
- flushing, sweating
GI:
- freq stool
- increased appetite
- feeding difficulties
- Hmegaly
- Smegaly
LABS:
- cholestasis
- thrombocytopenia
- hyper viscosity
- adv bone age
Risks to mom specific to pregnancy in neonatal graves
*Early labor / preterm birth
*Risk of pre-eclampsia
*Risk of thyroid storm
*Heart failure
when to do trabs in maternal graves
- 22weeks
- U/S if >2-3xUL
Familial non-autoimmune hyperthyroidism
- activating mutation of TSH-R
- AD
- increased thyroid size at variable age of presentation
TBG XS/Def syndromes
X-linked
total T3/T4 affect
free T3/T4 not affected
no tx
Familial dysalbuminemic hyperthyroxinemia
Mutation in albumin to have increased infinity for TH - so more binding
normal TSH, TT3, fT3, T3uptake
elevated TT4
normal free T4
no tx needed
what causes pretibial myxedema
deposition of glycosaminoglycan
thyroid function in pregnancy
- increased TBG
- increased type 3 deiodinase
- HCG homology with TSH - TSH-R stimulated (low TSH, high fT4)
what are the transporters in the thyroid follicular cell?
NIS - Na I symporter
PENDRID (Chloride Iodide transporter)
how long do drugs and Ab from mother last in baby
Drugs – 2-5 days
Ab – 3-6 months
congenital hypothyroidism DDx
1) Iodine deficiency
2) Iodine excess:
3) Transfer of Drugs or Antibodies Form Mother to Fetus
4) Transient Hypothyroxinemia of Prematurity
5) Hemangiomas
6) Defects in Thyroid Hormone Signaling Pathways
- Defects in Thyroid Hormone Metabolism
- Defects in Thyroid Hormone Transport Into Cells
- Defects in Thyroid Hormone Receptors
most common place for ectopic thyroid
sublingual
length of time neonatal graves
The usual clinical course of neonatal Graves disease extends from 3 to 12 weeks
goitre ddx
- chronic lymphocytic thyroiditis (Hashimoto)
- colloid goiter
- thyroid hormone resistance
- subacute or acute thyroiditis
- Graves disease
- congenital hypothyroidism. (dyshormonogenesis)
- iodine deficiency (endemic goitre)
- excessive iodine ingestion (Wolfe-Chaikoff effect)
- infiltrative dysorders
— histiocytosis
—cystinosis
—neoplasms (lymphoma, teratoma)
—adults: sarcoidosis, amyloidosis
aetiologies of 1ary hypoT
- Hashimoto (autoimmine)
- iodine deficiency/excess
- neck irradiation
- drugs
- syndromes
- infiltrative process
- cystinosis
- congenital
aetiologies 2ary hypoT
- hypopit
- cranial radiation
- CNS process (tumour, infection, injury)
- isolated TSH B gene mutation
drugs that increased clearance TH
phenobarbitol
phenytoin
carbamazines
oxcarbemazipine
rifampin
what decreases and increases TSH in hypothal-pit-thyr axis
decreases TSH:
- dopamine
- dopamine agonist (bromocriptine, carbegoline)
- glucocoirticoids
- opiates
- octreotide
increases TSH:
- hypocortisolism
- dopamine receptor blockers (meoclopramide)
what is Wolff chaikoff
when excess iodine
inhibits organification of iodine which decreases T4 and T3 synthesis
lab findings in hypoT other than TFTs
- hypercholesterolemia (incr LDL)
- hyponatremia (increased TBW)
- anemia (decr erythropoietin, decr O2 req)
- elevated CK and LDH (from skeletal muscle)
- reduced GFR
- elevated liver transaminases
- elevated PRL (TRH stim from the hypothalamus)
- decreased/impaired GH secretion
factors that make remission of graves less likely
thyroid gland is large (>2 times normal size for age),
the child is young (<12 years),
not Caucasian,
serum TRAb/TSI levels are elevated, or
the patient presents with profound hyperthyroidism at presentation
remission rate graves
30% in 1-2yrs
at what point if there is no remission from graves should you move on from ATD
2y
goal of RAI in GD
to induce hypothyroidism (not euthyroidism because increased risk of neoplasm)
how long after 131I treatment for the patient to become biochemically euthyroid or hypothyroid
6-12w
how to treat after 131-I for graves disease
BBlocker
what is the risk of recurrence after subtotal thyroidectomy in graves
hyperthyroidism recurs in 10% to 15% of patients
familial non-autoimmune hyperthroidism
activating mutation of the TSH receptor
myxoedema coma from hypothyroidism
-Altered LOC (semi/comatose)
-Dry, coarse skin
-hoarse voice
-thin scalp and eyebrow hair
-Hyperreflexic (hung reflexes)
-Pericardial, pleural, peritoneal effusions
-Marked hypothermia
-QT prolongation and Torsades
-Disorientation
-Depression
-Psychosis
Med conditions where thyroxine needs are increased
i) Nephrotic syndrome - due to increased urinary losses (mentioned in ATA guidelines)
ii) Celiac disease (mentioned in ATA guidelines)
iii) Vascular tumors (198), fibroblastic tumors (199), and gastrointestinal stromal tumors
iv) Consumptive hemangioma
v) Pregnancy
vi) Pseudohypoparathyroidism type 1
most common cause of congenital hypothyroidism
Maternal iodine deficiency (worldwide most common)
ii) Ectopic or absent thyroid (in iodine sufficient regions)
if you have graves ophthalmopathy, what’s the preferred tx
ATD, surgery
not RAI
what nerve to worry about TTx
Recurrent laryngeal nerve damage
what is strums ovarii
a variant of dermoid tumors of the ovary in which thyroid tissue components is the major constituent
can secrete thyroid hormone
what is silent thyroiditis
small painless goiter
thyrotoxic to hypothyroid to recovery
probably autoimmune
decrease RAI
Tx GO
i) Smoking cessation
**treat hyperlipidemia
ii) Refer to ophthalmology
iii) Symptom relief (topical lubrication, etc)
iv) Ensure rapid treatment of hyperthyroidism (since the sooner a patient is euthyroid the better the ophthalmopathy will be)
v) Avoid RAI (worsens outcomes)
vi) If RAI is done consider course of corticosteroids
vii) If thyroidectomy or RAI done, ensure rapid initiation of Synthroid (more time euthyroid improves outcomes)
viii) Consider elevating head of the bed and diuretics for periorbital edema
ix) Consider eye radiation therapy
SEvere:
- taping of eyelids at night
swimming goggles
what is TRH stimulation
you give IV TRH to a patient and measure TSH, FT4
primary hypothyroid: stimulates TSH but fT4 is low
pituitary: no rise in TSH
hypothalamic: TRH produces delayed (60-120min vs 15-30min) increase in TSH
(because TRH was deficient before, so TSH was not being made, so now it takes longer
b/c needs to be made from the start, rather than some present and released right away)
thyroid hormone resistance: both TSH and free thyroid hormones are high (b/c body
is not responding to free thyroid hormones so TSH ramping up)
remnant from thyroid budding
Foramen cecum
remnant from thyroid migration
thyroglossal duct
after RAI for hyperthyroidism, what to do
consider resuming MMI 3-7 days after RAI if symptomatic
Follow-up within the first 1–2 months after RAI
-> do free T4, total T3, and TSH
Biochemical monitoring should be continued at 4- to 6-week intervals for 6 months
Continue until stable hypothyroidism
how to prepare for surgery to Hyperthyroidism
what to do with meds
Render euthyroid
KI- containing preparation should be given in the immediate preoperative period
ATD should be stopped at the time of thyroidectomy for GD
b-adrenergic blockers should be weaned follow- ing surgery
Role of TSH in TH synthesisi
○ Iodide influx (cell), efflux (colloid)
○ TPO actions
○ Uptake of TG into cell
○ TH release into plasma
RAI S/E
§ Thyroid storm / exacerbation of hyperthyroidism
§ Worsening eye disease
§ Excessive tearing frorm eyes or dry eyes
§ Sialadenitis / swollen salivary glands
§ Dry mouth / insufficient salivary production
§ Neck tenderness and swelling
§ Nausea
§ Metallic taste in the mouth / losts of taste / taste change
what is the problem in GO
what cytokines
glycosaminoglycans
TNFa
IL6
meds w malabsorption of levothyroxine
Bile acid sequestrants
Phosphate binder
PPI
Calcium-containing
Iron-containing
Aluminum containing
Fiber supplements
Soy containing supplements
Simethicone
Raloxifene - post menopausal osteoporosis
signs that suggest Graves more than hashimotos in hyperT
Proptosis / Stare -> graves ophthalmology
Lid lag
Smooth and rubbery goiter
Pretibial myxedema - more common in Graves than Hashimotos
Labs:
Elevated TSH-stimulating immunoglobulins / TRAbs
High RAIU - is this a lab finding??
(fT4/fT3 - higher in Graves)
Other than thyroid, what tissues uptake RAI?
- lung
- salivary gland
- stomach
- breast
- urinary tract
