H_Review_Hypothyroidism Flashcards
Other Manifestations
Pituitary enlargment
Elevated Prolactin
Primary hypthyroidism causes
MC : Hashimoto’s thyroiditis / atrophic thyroiditis
surgery / RAI
Iodine def
Congenital (ectopic)
Drugs
Consumptive
TSH receptor antibodies
Free T4 index
Total T4 X THBR - total T4 X THBR
THBR = T3 resin uptake / control serum T3 resin uptake
Hashimoto’s encephalopathy
A relapsing encephalopathy occurring in association with Hashimoto’s thyroiditis, with high titers of anti-thyroid antibodies.
- personality changes/
- aggression /
- delusional behavior /
- concentration and memory problems /
- coma /
- disorientation /
- headaches /
- jerks in the muscles (myoclonus - 65% cases) /
- lack of coordination (ataxia - 65% cases) /
- partial paralysis on the right side /
- psychosis /
- seizures (60% cases) /
- sleep abnormalities (55% cases)
- speech problems (transient aphasia - 80% cases)
- status epilepticus (20% cases)
- tremors (80% cases)
Associated with Hashimoto’s
Thyroid Lymphomas
Thyroid autoimmunity - ameliorate ?
Selenium 200 mcg/d for 3 months / lowered TPO ab however does not indicate worsening or getting better.
Hashimotos’s and Iodine
Increased prevalence with increase iodine exposure
Iodine induced hypothyroidism : failure to escare from wolff chaikoff effect / block of iodine organification from excess iodine load
Amiodarone hypothyroidism
- Direct cytotoxic effect on the thyroid follicular cells / destructive thyroiditis
- Iodine induced damage to the thyroid follicles may accelerate the natural trend of Hashimoto thyroiditis towards hypothyroidism
- Can keep elevated iodine in body upto 9 months
- inhibits 1 5’ deiodinase enzyme activity - decreases T4-T3 conversion / patients may need a higher dose
Transient Hypothyroidism
Postpartum thyroiditis
Silent thyroiditis - hyperthyroid from the leakage then hypothyroid for a short period of time then normal T4 levels
Hypothyroidism due to thyroiditis
Painless (silent)
- Lymophcytic / TPO ab
- Postpartum (5-10%)
- Drugs Lithium / amiodarone / interferon alfa / interleukin2
Painful (subacute, granulomatous, de quervains)
- could be initially unilateral
- Elevated ESR +/- fever
- Viral or post viral
Lithium
- causing thyroid disorders?
Goiter
Most common / inhibition of thyroid hormone secretion results in decreased serum T4 and T3 concentrations, increase thyrotropin (TSH) a new steady state, secretion of a normal amount of thyroid hormone by an enlarged thyroid gland / first two yrs of treatment
Hypothyroidism
in the presence or absence of goiter, usually subclinical; / high TSH and normal T4 and T3. A few patients have overt hypothyroidism with all of its usual symptoms and signs.
increases intrathyroidal iodine content, inhibits the coupling of iodotyrosine residues to form iodothyronines (thyroxine [T4] and triiodothyronine [T3]), and inhibits release of T4 and T3. (See ‘Introduction’ above.)
Chronic autoimmune thyroiditis
patients who develop hypothyroidism during lithium treatment have underlying chronic autoimmune thyroiditis
lithium itself can induce thyroid autoimmunity is unknown
Hyperthyroidism
In two retrospective studies, the frequency of hyperthyroidism in patients treated with lithium was more than two to three times greater than that of hyperthyroidism in the general population
High GAD antibodies
Glutamic acid decarboxylase (GAD) is a neuronal enzyme involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA). Antibodies directed against the 65-kd isoform of GAD (GAD65) are seen in a variety of autoimmune neurologic disorders including
- stiff-man (Moersch-Woltman) syndrome
- autoimmune cerebellitis
- brain stem encephalitis
- seizure disorders
- neuromyelitis optica and other myelopathies
- myasthenia gravis
- Lambert-Eaton syndrome
- Dysautonomia
Lithium thyroid treatment
Hyperthyroidism
Its effects on thyroid hormone secretion are quantitatively similar to those of iodide, and it therefore may be given in place of iodide in patients who would benefit from rapid correction of hyperthyroidism but are allergic to iodine
Prolongs the retention of radioiodine within the thyroid gland, which could increase the effectiveness of radioiodine therapy
Thyroid cancer
When patients with thyroid cancer are treated with 131-I, it is sometimes helpful to increase retention of the isotope by cancer tissue
Sunitinib
Current uses : GIST& renal cell carcinoma
- Causes a destructive hypothyroidism
- Increase requirement for thyroid hormone in athyreotic patients
Uptake is low / could be thyroiditis vs hypothrophy
Bexarotene
Retinoid X receptor agonist
Hypothyroidism - Central Hypothyroidism
Also increase peripheral degradation of thyroid hormone (no rise in TSH)
Levothyroxine
7 day Half life
Levothyroxine brand names
- Levothriod
- Levoxyl
- Synthroid
- Tirosint (gel cap)
- Unithyroid
Levothyroxine dosing
1.6 ug/kg/day
Start low on elderly and CAD 12.5-25 mcg
Subclinical hypothyroidism may only need 50 mcg/day
Fluctuating levels
Worry about if
- Worsening hypothyroidism (hashimoto’s)
- Increase clearance
- Impaired absorption
- Drugs blocking FT4-FT3 conversion (amio)
- Pregnancy
- Estrogen (OCP, HRT)
- Compliance
LT4 impaired absorption by
- Antacids
- Iron
- Calcium
- Cholestyramine
- Sucralfate
- Sucralfate
- Raloxifene
- PPI
- Celiac Dz
LT4 Clearance
Phenytoin
Carbamazepine
Rifampin
Phenobarbital
Sertraline
TKI
Myxedema Coma
Obtundation coma
Hypthermia
Brady
Hypoventilation
Subclinical hypothyroidism
LDL
CAD
LDL increases - benefits not know to treat
CAD ?
Subclinical Hypothyroid - who to treat
Who no to treat?
TSH > 10
Hypothyroidism Pregnancy
TSH goals
FT4 / FT3 goals
TSH < 2.5 - 2nd and 3rd
- if hypothyroid miss period increase dose by 30 % or two additional doses per week
- TSH monitor Q4W first half of pregnancy then once between 26-32 weeks
FT4/Ft3 ~ 1.5 times
Things good to know
- MCC cause of hypothyroidism is iodine def worldwide
- Anti TPO antibodies are present in 98% of pt with autoimmune thyroid dz
- Low or normal TSH does not exclude the dx of hypothyroidism - central or drug induced (bexarotene) hypothyroidism is possible
- Annual risk of developing overt clinical hypothyroidism in pt with +ve TPO ~ 4%
Intrinsic drug effects Amiodarone
Intrinsic drug effects
●Amiodarone inhibits outer ring 5’-monodeiodination of thyroxine (T4), thus decreasing triiodothyronine (T3) production; reverse T3 accumulates since it is not metabolized to T2 [5].
●Amiodarone, and particularly the metabolite desethylamiodarone, blocks T3-receptor binding to nuclear receptors [6] and decreases expression of some thyroid hormone-related genes [7].
●Amiodarone may have a direct toxic effect on thyroid follicular cells, which results in a destructive thyroiditis [8].
Thyroid Amiodarone - risk factors
Predictors of risk
Autoimmune thyroid disease are at highest risk for amiodarone-induced hypothyroidism (due to failure to escape from the Wolff-Chaikoff effect).
Nodular goiter are at increased risk of type 1 amiodarone-induced thyrotoxicosis (AIT). The excess iodine from the amiodarone provides increased substrate, resulting in enhanced thyroid hormone synthesis and hyperthyroidism.
Destructive thyroiditis (type II AIT) typically occurs in patients with no underlying thyroid disease.
Dietary iodine intake also affects an individual’s risk of amiodarone-induced thyroid dysfunction. In iodine-sufficient areas, amiodarone-induced hypothyroidism appears to be more common than hyperthyroidism. In contrast, amiodarone-induced hyperthyroidism (usually type I AIT) is more common than hypothyroidism in iodine-deficient regions.
Management — The management of amiodarone-induced hypothyroidism is essentially the same as for any patient with hypothyroidism, although higher doses of thyroxine may be required to normalize the serum thyroid-stimulating hormone (TSH) level. The mainstays of therapy for amiodarone-induced hyperthyroidism are thionamides and glucocorticoids for type I and type II AIT, respectively.
Hypothyroidism — Transient changes in thyroid function tests often occur in euthyroid individuals treated with amiodarone. While most patients remain euthyroid during amiodarone therapy, patients with pre-existing autoimmune thyroid disease (subclinical Hashimoto’s thyroiditis or positive antithyroid antibodies) are at increased risk of developing amiodarone-induced hypothyroidism. The diagnosis and treatment of these patients is the same as for other patients with primary hypothyroidism.
●We suggest continuing amiodarone therapy in patients who develop amiodarone-induced hypothyroidism (Grade 2C).
●Euthyroidism should be restored by replacement with thyroid hormone. Thyroid hormone, in doses larger than normal, is often required. (See ‘Treatment’ above.)
●Amiodarone should only be discontinued if it fails to control the underlying arrhythmia. If amiodarone is discontinued in a patient without pre-existing autoimmune thyroid disease, the hypothyroidism often resolves.
Hyperthyroidism — There are two types of amiodarone-induced thyrotoxicosis (AIT). In type 1, there is increased synthesis of thyroid hormone, whereas in type 2 there is excess release of T4 and T3 due to a destructive thyroiditis. However, it is often difficult to distinguish between the two types and some patients may have elements of both. The 24-hour radioiodine uptake is typically not able to distinguish between types I and II AIT because the high levels of ingested iodine with amiodarone results in 24-hour uptakes of less than 1 percent in most patients with either type I or type II AIT. Color flow Doppler sonography may be the best way of distinguishing between the two types of AIT. (See ‘Differentiating the two types’ above.)
●In patients who develop AIT in whom the amiodarone was prescribed for life-threatening ventricular arrhythmias (and is effective), we suggest continuing the amiodarone and simultaneously treating the hyperthyroidism (Grade 2C). (See ‘Should amiodarone be discontinued?’ above.)
●If the amiodarone was not prescribed for life-threatening ventricular arrhythmias (or is ineffective), we suggest discontinuing the drug (Grade 2C). This should only be done in consultation with the patient’s cardiologist if alternative antiarrhythmics can be used. For type I AIT, amiodarone should not be discontinued until hyperthyroid symptoms are well controlled with thionamides, since worsening hyperthyroid symptoms due to increased T3 levels may occur when the amiodarone is discontinued. (See ‘Should amiodarone be discontinued?’above.)
Type I AIT — Type I AIT is hyperthyroidism with increased synthesis of T4 and T3; the excess iodine provides increased substrate, resulting in enhanced thyroid hormone production.
●We suggest thionamides as our first choice of therapy to treat type I AIT (whether amiodaroneis continued or discontinued) (Grade 2B). (See ‘Thionamides’ above.) Although radioiodine ablation has been reported to have been used (in rare patients with high enough radioiodine uptake), this is usually not an option due to low radioiodine uptake in the majority of type I patients. (See ‘Radioiodine’ above.)
Higher than average doses of thionamides are usually needed (30 to 40 mg of methimazole or 450 to 600 mg propylthiouracil [PTU] daily). Perchlorate or lithium are sometimes added to speed recovery, however, perchlorate is not available in the United States. In addition, perchlorate has been associated, albeit rarely, with aplastic anemia. (See ‘Thionamides’above.)
●Some patients are refractory to antithyroid drug therapy; they should be treated by thyroidectomy. When balancing the risk of a surgical procedure during careful cardiovascular monitoring with the risk of several months of unmonitored and uncontrolled thyrotoxicosis, the advantages of surgery in this setting become compelling. (See ‘Surgery’ above.)
Type II AIT — Type II AIT is a destructive thyroiditis that results in the release of excess T4 and T3, but not increased synthesis. It is typically seen in patients without underlying thyroid disease, and is caused by a direct toxic effect of amiodarone on the thyroid gland. The hyperthyroid phase may last from several weeks to several months, and is often followed by a hypothyroid phase and then recovery.
●For patients who develop type II AIT, we suggest glucocorticoid therapy as our first-line drug (whether amiodarone is continued or discontinued) (Grade 2B). (See ‘Glucocorticoids’ above.)
We typically start with prednisone (40 to 60 mg/day), and continue therapy for one to two months before tapering (to avoid exacerbations of hyperthyroidism). (See ‘Glucocorticoids’above.)
Thyroid amiodarone - managment
Management —
The mainstays of therapy for amiodarone-induced hyperthyroidism are thionamides and glucocorticoids for type I and type II AIT, respectively.
Hypothyroidism —
We suggest continuing amiodarone therapy in patients who develop amiodarone-induced hypothyroidism
Euthyroidism should be restored by replacement with thyroid hormone. Thyroid hormone, in doses larger than normal, is often required.
Amiodarone should only be discontinued if it fails to control the underlying arrhythmia. If amiodarone is discontinued in a patient without pre-existing autoimmune thyroid disease, the hypothyroidism often resolves.
Hyperthyroidism
- Type 1, increased synthesis of thyroid hormone in MNG
- Type 2 there is excess release of T4 and T3 due to a destructive thyroiditis.
The 24-hour radioiodine uptake is typically not able to distinguish between types I and II AIT because the high levels of ingested iodine with amiodarone results in 24-hour uptakes of less than 1 percent in most patients with either type I or type II AIT.
Color flow Doppler sonography may be the best way of distinguishing between the two types of AIT. (increased vascularity in type I
In pt prescribed for life-threatening ventricular arrhythmias continue the amiodarone and simultaneously treating the hyperthyroidism
if not prescribed for life-threatening ventricular arrhythmias / discontinuing the drug in consultation with the patient’s cardiologist
IN Type I AIT, amiodarone should not be discontinued until hyperthyroid symptoms are well controlled with thionamides, since worsening hyperthyroid symptoms due to increased T3 levels may occur when the amiodarone is discontinued.
Type I AIT
Type I AIT is hyperthyroidism with increased synthesis of T4 and T3; the excess iodine provides increased substrate, resulting in enhanced thyroid hormone production.
Thionamides as our first choice of therapy to treat type I AIT / Although radioiodine ablation has been reported to have been used this is usually not an option due to low radioiodine uptake in the majority of type I patients.
Higher than average doses of thionamides are usually needed (30 to 40 mg of methimazole or 450 to 600 mg propylthiouracil [PTU] daily). Perchlorate or lithium are sometimes added to speed recovery, however, perchlorate is not available in the United
Some patients are refractory to antithyroid drug therapy; they should be treated by thyroidectomy.
**Type II AIT **
Type II AIT is a destructive thyroiditis that results in the release of excess T4 and T3, but not increased synthesis. It is typically seen in patients without underlying thyroid disease, and is caused by a direct toxic effect of amiodarone on the thyroid gland. The hyperthyroid phase may last from several weeks to several months, and is often followed by a hypothyroid phase and then recovery.
For patients who develop type II AIT, we suggest glucocorticoid therapy as our first-line drug (whether amiodarone is continued or discontinued) (Grade 2B). (See ‘Glucocorticoids’ above.)
We typically start with prednisone (40 to 60 mg/day), and continue therapy for one to two months before tapering (to avoid exacerbations of hyperthyroidism).
