Thyroid Flashcards
Thyroid Hormone
- Affects function of every organ system
- Critical for normal growth and development in childhood
- Maintains metabolic stability in adults
Active unbound (free) thyroid hormone
- Diffuses into cells
- Elicits biologic effects
- Regulates thyrotropin/thyroid stimulating hormone (TSH) secretion (involves in negative feedback)
T4
ONLY source is secretion from thyroid gland
5’ monodeidonase enzymes
- Catalyzes T4 to T3 in extra-thyroid peripheral tissues
Type 1 5’-monodeidonase enzymes
- Converts T4 to T3 in **liver **
- Also present in kidney and thyroid
- Predominant extrathyroidal source of T3
Type 2 5’-monodeidonase enzymes
- Converts T4 and T3 in **pituitary **
- Also present in thyroid, CNS, and borwn adipose tissue
- Intracellular T3 production -** important in hypothyroidism/iodine deficiency **
Type 3 5’-monodeidonase enzymes
Present in placenta, developing brain, and skin
HPA
- Highly sensitive to small changes in circulating thyroid hormone concentrations
- Alterations in thyroid hormone secretion maintain peripheral free thyroid hormone levels within a narrow range
- Recall that this is influenced by negative feedback
Thyroid Hormone Transport Proteins
- Transport T4 and T3 in the bloodstream
- Assure minimal urinary loss of iodine (one of the trace elements)
- Provide mechanism for uniform tissue distribution of free hormone
- Transport hormones into CNS
What are the transport proteins?
- Thyroxine-binding globulin (TBG)
- Transthyretin (TTR)
- Albumin
What blocks the transfer of iodine transfer into thyroid?
- Bromine
- Fluorine
- Lithium – under certain circumstances
What inhibits thyroid hormone secretion?
- Iodine – in large doses
- Lithium
What impairs organification and coupling of thyroid hormones?
- Thioamides
- Sulfonamide
- Salicylamide
- Antipyrine
Iodine deficiency
Causes INCREASE in MIT:DIT ratio–> relative INCREASE in T3
What competitively inhibits transport (structurally related)?
- Thiocyanate
- Perchlorate
- Pertechnetate
What is extrathyrodial deiodination of T4 and T3 impacted by?
- Nutrition
- Nonthyroidal hormones
- Ambient temperature
- Drugs
- Illness
Thyrotoxicosis
Caused by tissue exposure to excessive levels of T4, T3, or both
Radioactive iodine uptake (RAIU)
- Measurement of radioactive iodine uptake (RAIU)
- Normal 24-hour range 10-30%
- Elevated RAIU indicates endogenous hyperthyroidism – thyroid gland actively overproducing T4 or T3
- Low RAIU in absence of iodine excess indicates that high levels of thyroid hormone are not a consequence of thyroid gland hyperfunction
What is the diagnostic criteria?
- Low serum TSH
- Elevated serum free and total T4 and T3
- RAIU
- Elevated uptake by thyroid gland when hormone is being overproduced
- Suppressed uptake in thyrotoxicosis due to thyroid inflammation (thyroiditis)
What are some other test for thyrotoxicosis?
- Thyroid-stimulating antibodies (TSAbs)
- Differentiates autoimmune thyrotoxicosis (Graves’ disease) and everything else
- Thyroglobulin
- Thyrotropin receptor antibodies
What are some symtpoms of thyrotoxicosis?
- Hyperactivity/irritability/dysphoria
- Heat intolerance/sweating
- Palpitations
- Fatigue/weakness
- Weight loss with increased appetite
- Diarrhea
- Polyuria
- Menstrual disturbances of libido
What are signs of thyrotoxicosis?
- Tachycardia – atrial fibrillation in elderly
- Tremor (fine tremor of protruded tongue/outstretched hands)
- Thyromegaly/goiter
- Warm, moist skin
- Muscle weakness/proximal myopathy
- Lid retraction/lag
- Gynecomastia
- Fine hair
- Onycholysis
- Cardiovascular: tachycardia at rest, widened pulse pressure, systolic ejection murmurHyperactive deep tendon reflexes
What are the signs of Graves’ disease?
- Ophthalmopathy/exophthalmos
- Pretibial myxedema
What are the presentation of thyrotoxicosis dependent on?
- Thyrotoxicosis severity
- Duration
- Individual susceptibility to excess thyroid hormone
- Patient age
- Elderly: symptoms may be masked, patients may present with fatigue and weight loss
What are the presentations of Thyroid storm?
- Tachycardia
- Heart failure
- Psychosis
- Hyperpyrexia
- Coma
What are some causes of Primary Hyperthyroidism?
*** Graves’ disease
* Toxic multinodular goiter
* Toxic adenoma **
* Functioning thyroid carcinoma metastases
* Activating mutation of TSH receptor
* Activating mutation of GSalpha
* Struma ovarii
* Drugs: iodine excess
What are the causes of thyrotoxicosis without hyperthyroidism?
- Subacute thyroiditis
- Silent thyroiditis
- Thyroid destruction:
- Amiodarone
- Radiation
- Infarction of adenoma
- Ingestion of excess thyroid hormone (thyrotoxicosis factitial) or thyroid tissue
What are the causes of secondary hyperthyroidism?
- TSH-secreting pituitary adenoma
- Thyroid hormone resistance syndrome
- Occasional patients may have features of thyrotoxicosis
- Chronic gonadotropin-secreting tumors
- Gestational thyrotoxicosis
Primary thyrotoxicosis
Low TSH and high unbound T4
Secondary thyrotoxicosis
TSH normal or elevated, high unbound T4
Graves’ Disease
Autoimmune syndrome causing hyperthyroidism due to action of thyroid-stimulating antibodies (TSAbs) directed against thyrotropin receptor on surface of thyroid cell
What are the classical findings of Graves’ Disease
- Hyperthyroidism
- Diffuse thyroid enlargement
- Exophthalmos
- Less commonly expressed as:
- Pretibial myxedema
- Thyroid acropachy
What are some characteristics of Graves’ Disease
- Thyroid gland diffusely enlarged
- Gland surface can be smooth or bosselated
- Consistency varies from soft to firm
- Thrill/systolic bruit may be present in severe disease
- Increased vascularity with hyperplasia
What are some laboratory findings of Graves’ disease?
- Increase in T3 relative to T4 (increase ratio)
- T3 toxicosis
- T4 toxicosis
- Saturation of TBG increased
- TSH levels suppressed or undetectable
*** TRAbs **
How do you diagnose Graves’ disease?
1) Measure serum-free T4, total T4, total T3 and TSH to confirm diagnosis of thyrotoxicosis
2) 24-hr RAIU when diagnosis is uncertain AND patient is not pregnant/lactating
3) Measure TRAb to differentiate Graves disease from other causes of thyrotoxicosis
What is the treatment of Graves’ Disease?
- Antithyroid medications
- Radioactive iodine
- Surgery
When does Graves’ Opthalmopathy occur?
Within the year before or after diagnosis of thyrotoxicosis in 75% of patients
What are some features of Graves’ Ophthalmopathy?
- Lid retraction
- Periorbital edema
- Chemosis
- Conjunctival injection
- Proptosis – abnormal protrusion/displacement of eye (bug eye)
What are some early manifestations of Graves’ Ophthalmopathy?
- Grittiness
- Eye discomfort
- Excess tearing
What is the pathway to Graves’ Ophthalmopathy?
1) Extraocular muscle infiltrated by activated T cells
2) Cytokines released
3) Fibroblast activation
4) Increased synthesis of glycosaminoglycans
5) Increased water leads to muscle swelling
Toxic Adenoma
- Autonomous thyroid nodule – discrete thyroid mass functioning independent of pituitary and TSH control
- Hot nodule
- Benign tumors that produce thyroid hormone
What are some treatment options of toxic adenoma?
- Surgical resection
- Antithyroid drugs
- Percutaneous ethanol injection (not often used in practice)
- Associated with pain and damage to surrounding extrathyroid tissue
- Radioactive iodine ablation
- Rarely associated with thyroid cancer
- Conservative management possible if nodule not large enough to cause thyrotoxicosis
What do you give a patient when he/she is euthyroid who have goiter?
- Thioamides
- Dosed to suppress TSH levels to:
- Slow goiter growth
- Cause shrinkage
- Dosed to suppress TSH levels to:
Therapy goal is to reduce goiter size and mass-related dysphagia
What is the preferred treatment of multinodular goiter?
- RAI (radioactive iodine)
- Surgery appropriate
- Younger patients
- Goiter is impinging on vital organs
- Alternate treatment: percutaneous injection of 95% ethanol to destroy single/multinodular adenomas (not often used in practice)
- 5-year success rate approaches 80%
What are the less common causes of thyrotoxicosis?
- Trophoblastic disease
- TSH-induced hyperthyroidism
- Pituitary resistance to thyroid hormone
- Subacute thyroiditis
- Painless thyroiditis
- Thyroid cancer
- Struma Ovarii
Trophoblastic disease
Human chorionic gonadotropin (hCG) is a stimulator of TSH receptor and may cause hyperthyroidism due to similarities in alpha subunits (the two hormones have unique beta subunits)
What is the criteria for diagnosis of TSH-induced hyperthyroidism?
- Evidence of peripheral hypermetabolism
- Diffuse thyroid gland enlargement
- Elevated free thyroid hormone levels
- Elevated or inappropriately “normal” serum immunoreactive TSH concentrations
TSH-secreting pituitary adenoma
- Occurs sporadically
- Release biologically active hormones unresponsive to normal feedback control
- Co-secrete prolactin or growth hormone
- Patients may present with amenorrhea/galactorrhea or signs of acromegaly
What is the presentation of TSH-secreting pituitary adenoma?
- Visual field defects – tumor impingement of optic chiasm by tumor
What is the diagnosis of TSH-secreting pituitary adenoma?
- Demonstration of a lack of TSH response to THR stimulation
- Lack of routine availability of TRH
- Inappropriate TSH levels
- Elevate alpha-subunit levels
- Radiologic imaging
What is the treatment of TSH-secreting pituitary adenoma?
Transsphenoidal pituitary surgery is treatment of choice
* Pituitary gland irradiation often given post surgery to prevent tumor recurrence
* Medications: dopamine agonists and octreotide have been used to treat tumors
- Especially when prolactin is co-secreted
Subacute Thyroiditis
- Painful subacute thyroiditis often develops after viral syndrome
- Genetic predisposition – higher risk for patients with **HLA-Bw35 antigen **
What are the presentations of subacute thyroiditis?
- Systemic symptoms: fever, malaise, myalgia
- Typical thyrotoxicosis signs and symptoms
- Severe pain in thyroid region
- May extend to ear on affected side
- Pain migrates from one side of gland to other with time
- Physical exam: thyroid gland firm and exquisitely tender
What is the treatment for subacute thyroiditis?
- Thyrotoxic symptoms may be relieved with beta-blocker
- Pain: NSAIDs
- Prednisone (30-40 mg daily) may be used to suppress inflammatory process if needed
- Anti-thyroid drugs NOT indicated – do NOT decrease release of preformed thyroid hormones
Postpartum thyroiditis
- Development of lymphocytic thyroiditis during the first 12 months AFTER end of pregnancy
What is the treatment of painless thyroiditis?
- Propranolol/metoprolol – adrenergic symptoms
- Anti-thyroid drugs not indicated as they do NOT DECREASE release of performed thyroid hormones
Thyrotoxicosis factitial
Hyperthyroidism due to ingestion of thyroid hormone
What medications induce thyrotoxicosis?
- Amiodarone
- Biotin
Amiodarone
- Thyrotoxicosis: 2-3%
- Overt hypothyroidism: 5%
- Subclinical hypothyroidism: 25%
- Euthyroid hyperthyroxinemia
- Contains 37% iodine by weight
