​Kembara Xtra - Medication - Graves Disease

​Kembara Xtra - Medication - Graves Disease 
Introduction 
Thyroid-stimulating hormone receptor (TSHR) activation by thyrotropin receptor antibodies (TRAb) results in increased thyroid hormone production in autoimmune illness. the most typical reason for hyperthyroidism. Thyrotoxicosis, diffuse goiter, ophthalmopathy (orbitopathy), and sporadically localized dermopathy (pretibial myxedema) are considered classic features.

Epidemiology Incidence: Occurs in 0.2% of pregnancies, of which 95% are attributable to Graves disease; Annual incidence of 20 to 50 instances per 100,000 individuals; Peaks between 30 and 50 years of age, however people can be affected at any age.
Prevalence
Graves disease causes 60-80% of all instances of hyperthyroidism in the United States, with a prevalence of 2% for women and 0.2% for men. Similar terms: von Basedow illness

Pathophysiology and Etiology 
An excessive amount of thyroid-stimulating hormone (TSH) receptor antibodies are produced by B cells, mostly in the thyroid, which is probably caused by a genetic defect in suppressor T cells.

These antibodies bind to TSH receptors in the thyroid, activating the receptor and promoting the synthesis and secretion of thyroid hormones as well as thyroid development (resulting in goiter).
Ocular symptoms are brought on by binding to a related antigen in the connective tissue of the retro-orbit.

Genetics: Twin studies reveal a 20% concordance rate, and there is a higher chance if there is a personal or family history of any autoimmune condition, including Hashimoto thyroiditis.

Risk Elements 
Gender (5–10 times more women than men)
Family history (15% of Graves disease patients have an afflicted relative) and postpartum period

Iodine, amiodarone, lithium, highly active antiretroviral therapy (HAART), and occasionally immune-modulating drugs (like interferon therapy)
Smoking (increased chance of ophthalmopathy development)

Prevention 
It is not advised to screen for TSH in people who are asymptomatic.


Mitral valve prolapse, Type 1 diabetes, Addison disease, hypokalemic periodic paralysis, vitiligo, alopecia areata, and other autoimmune diseases are all associated conditions.


Diagnosis: Hyperactivity, anxiety, emotional lability, sleeplessness, palpitations, tachycardia, sweating, heat intolerance, pruritus, skin changes, and weight loss with increased appetite
Exhaustion and dyspnea (caused by muscle weakness)
Loose, frequent stools, blurred vision or diplopia, lacrimation, photophobia, a gritty feeling in the eyes (ocular dryness), retro-orbital discomfort, painful eye movement, loss of color vision or visual acuity, worsening of chronic medical conditions (anxiety, bipolar disorder, glucose intolerance, heart failure, or angina), among other symptoms.
Aspects of Geriatrics
Patients who are elderly may not exhibit the typical symptoms; they may also have atrial fibrillation, weight loss, or shortness of breath.

clinical assessment 
Ophthalmologic symptoms, which are present in 50% of cases, include grittiness or discomfort in the eyes, retrobulbar pressure or pain, lid lag or retraction, proptosis, ophthalmoplegia, papilledema, and possible loss of color vision.
Enlarged (goiter), non-tender, and free of nodules thyroid gland; potential bruit (increased blood flow)
Fine hair, heated skin, brittle nails, finger clubbing, suspected pretibial myxedema (orange peel appearance), and possible hyperpigmented plaques (dermopathy) are integumentary symptoms.
Cardiac: probable atrial fibrillation, hyperdynamic circulation, and resting tachycardia

 Proximal myopathy, fine tremor, hyperreflexia, and, in rare cases, soft tissue edema of the extremities and clubbing of the digits (acropachy)

Differential Diagnosis: Toxic adenoma or toxic multinodular goiter
Thyroiditis (hormone leakage) is an acute, damaging condition that is typically caused by a virus. The thyroid will be sensitive.
Antithyroperoxidase [TPO] antibodies may stimulate TSH receptors in lymphocytic conditions, including postpartum - Hashimoto thyroiditis.
Iatrogenic (treatment-related) – Iodine-induced (through diet, radiographic contrast, or pharmaceuticals)
Thyroid hormone overreplacement (intentional or unintentional) brought on by amiodarone
Pituitary adenoma-producing tumor-specific TSH
- Tumors that produce hCG (human chorionic gonadotropin; activate TSH receptors)
- The synthesis of thyroid hormone outside of the thyroid gland (as in struma ovarii or metastatic thyroid cancer).

Laboratory Results 
Initial examinations (lab, imaging)

The first test is TSH, which is suppressed (low or undetectable).

TSH 0.1 mU/L confirms probable thyroid illness with >98% sensitivity and >92% specificity.
A low TSH and elevated free T4 indicate hyperthyroidism.
T3 may be raised alone, together with free T4, in a condition called T3 toxicosis.
Tests in the Future & Special Considerations
It may be possible to distinguish between Graves disease and toxic multinodular goiter using thyroid peroxidase antibodies (found in 70–80% of patients with Graves disease) and TSH receptor antibodies (thyroid binding inhibitory immunoglobulin).

pregnant women's issues
The rise in total T4 and T3 during the first half of pregnancy is caused by an increase in serum T4-binding globulin concentration and an initial activation of TSH by hCG. The TSH level decreases over the course of pregnancy, thus it should be compared to the ranges for each trimester.
If the diagnosis of Graves is not apparent during pregnancy, the thyrotropin receptor autoantibody (TRAb) test should be utilized. It is positive in 95% of patients with Graves.

● During pregnancy, ultrasonography is the main imaging technique.

Other/Diagnostic Procedures
Perform a radioactive iodine uptake (RAIU) and scan after verifying suppressed TSH and high T4. In contrast to localized/nodular elevated uptake in adenoma and multinodular goiter and decreased uptake in thyroiditis or exogenous thyroid hormone, patients with Graves disease would show diffuse, elevated RAIU.
To differentiate between nodular autoimmune causes of hyperthyroidism and nodular types of Graves disease, a thyroid ultrasound may be performed.


Management 
The medical provider and the patient jointly decide on the therapy modality to be used. The aim is to rectify the hypermetabolic condition with the least amount of side effects and post-treatment hypothyroidism occurrence.

First Line of Medicine
Methimazole (MMI) and propylthiouracil (PTU) are antithyroid medications that compete with the thyroid for iodine, reducing the thyroid's ability to synthesize thyroid hormone. Propylthiouracil prevents the peripheral conversion of T4 to T3, which is a side effect of antithyroid medication.
- Alternative therapy for children and adults who reject RAI
- Older or cardiac patients may receive this as a pretreatment prior to RAI or surgery. Except for the first trimester of pregnancy, methimazole is currently nearly entirely utilized. Its increased duration of action enables once-daily dose, quicker effectiveness, and fewer adverse effects.
– Use the lowest dose of methimazole that is still effective.
Skin rash (3-5%), fever, arthralgias, and GI side effects are minor side effects that can be managed by moving from one drug to another.
- Polyarthritis (1-2%), idiopathic granulocytopenia (0.5%), and cholestasis/jaundice (rare) are significant adverse effects that call for a change in therapy.
– The best time to use antithyroid medications is between 12 and 18 months; there is no added benefit to treatment beyond 18 months (4)[A].
Up to 50% of patients who initially respond to treatment experience relapse; rates are higher in smokers, those with large goiters, or those who test positive for thyroid-stimulating antibodies at the end of therapy. Radioactive iodine (RAI) concentrates in the thyroid gland and destroys thyroid tissue. Radioiodine plus prednisone therapy may have the lowest risk of exacerbating or developing a new case of ophthalmopathy.
- In the absence of significant or severe orbitopathy, the treatment of choice for hyperthyroidism final therapy– Risks include side effects (neck soreness, flushing, decreased taste), worsening ophthalmopathy (15% incidence, higher in smokers), posttreatment hypothyroidism (80% incidence, not dose dependent), radiation thyroiditis (1% incidence), and the need to follow safety precautions until radiation is eliminated from the body. Pretreatment with antithyroid medication should be taken into consideration in patients with severe disease and the elderly, to lower the risk of posttreatment transient hyperthyroidism.
– Repeatable in as little as 3 months if there is a minor response or in 6 months if the thyroid is not euthyroid.

Referral: Endocrinologist for RAI therapy; if patient is pregnant or nursing; Ophthalmologist for Graves ophthalmopathy; Surgeon for blockage or cosmesis if medication therapy has failed or patient refuses RAI.


Further Treatments 

Blockers offer quick relief from adrenergic symptoms for Graves hyperthyroidism; begin treatment while the workup is ongoing.
Most frequently, long-acting propranolol (40–160 mg/day) is used to treat symptoms.
– Iodides, which prevent the conversion of T4 to T3 and restrain the release of TSH, can be used to reduce symptoms.
When rapid control of thyrotoxicosis is required, IV corticosteroids are used because they inhibit deiodinase type 2, which prevents the conversion of T4 to T3. They should not be used long-term (as this may result in a paradoxical increase in TSH release) or in combination with antithyroid medications.
– In addition to antithyroid medications, bile acid sequestrants are employed; their action is the binding of thyroid hormones in the enterohepatic circulation.

Graves ophthalmopathy can be treated with lubricants, nocturnal ointments, botulinum toxin injections for upper lid retraction, and quitting smoking. For corneal protection, colored glasses when outside, artificial tears, and patching or taping the lids at night are recommended.
If there are no contraindications, moderate to severe cases should be treated with pulsedose IV glucocorticoids.
Prednisone 60 to 80 mg/day for two to four weeks, then taper off, is an alternative.
- Teprotumumab, a fully humanized monoclonal antibody inhibitor of insulin-like growth factor 1 receptor, has recently been approved by the FDA for use in patients with moderate to severe ophthalmopathy. - Compressive optic neuropathy is a medical emergency that is treated with a combination of IV glucocorticoids, orbital irradiation, and surgical decompression.

Use medium- to high-potency topical corticosteroids with an occlusive dressing for Graves dermopathy.

Procedures Thyrotoxicosis that is persistent or recurring, diffusely enlarged thyroid with compressive symptoms, concomitant hyperparathyroidism or thyroid malignancy, nodular thyroid, active Graves' ophthalmopathy, and second-trimester pregnancy are all indications for thyroidectomy.

In individuals with Graves disease, total thyroidectomy (TT) is comparable to subtotal thyroidectomy (ST) in terms of postoperative hazards, which also include ophthalmopathy progression, hemorrhage, permanent hypoparathyroidism, and recurrent laryngeal nerve palsy. However, TT causes a rise in transient hypoparathyroidism and is linked to a decreased likelihood of recurrent hyperthyroidism.


ICU admission for severe hemodynamically compromised thyrotoxicosis (thyroid storm)
CONTINUING CARE AFTERCARE RECOMMENDATIONS
patient observation
TSH and T4 levels should be checked every one to two months for the first six months following treatment, then every three months for a year, and then every six to twelve months after that. Check the CBC every year for patients receiving methimazole and propylthiouracil therapy. Check anti-TSH receptor antibodies after a year of treatment to see if you can stop using the medicine.

Pregnant women's issues
RAI is not advised during pregnancy or while nursing.
Because methimazole might cause birth defects, propylthiouracil is chosen during the first trimester of pregnancy. Due to the possibility of PTU-induced liver damage, switch to methimazole in the second and third trimesters.

Women who are not receiving therapy frequently experience postpartum hyperthyroidism aggravation, thus TSH and symptoms should be closely watched.

Modification of Lifestyle 

compliance with medication and follow-up surveillance schedules


Prognosis: Generally favorable with therapy, while it may have permanent effects on the eyes, heart, and mind. Increased morbidity and mortality due to osteoporosis, atherosclerosis, obesity and insulin resistance, endothelial cell dysfunction, and thromboembolic risk.

Complications 
The proportion of Graves disease patients who develop hypothyroidism within the first year of treatment varies depending on the type of therapy.

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