​Kembara Xtra - Medicine - Hyperthyroidism

​Kembara Xtra - Medicine - Hyperthyroidism 
A range of clinical signs that are associated with excess thyroid hormone are known as hyperthyroidism or thyrotoxicosis. While the latter can also be created from another source, the former refers to excess from the thyroid gland.
● Thyrotoxicosis patients typically have hyperthyroidism. This isn't always the case, though.
Patients may experience radiation-induced thyroiditis, exogenous thyrotoxicosis, subacute thyroiditis, and thyrotoxicosis.
The most prevalent form is Graves disease (GD), which is characterized by widespread goiter and thyrotoxicosis.
Up to 50% of patients have infiltrative orbitopathy.
Rare cases of infiltrative dermopathy exist (1). The thyroid-stimulating hormone (TSH) receptors are the target of autoantibodies.
Toxic multinodular goiter (TMNG): second most prevalent; most common cause of hyperthyroidism in people older than 65; patients older than 40; sneaky onset; common in iodine-deficient locations.
Younger patients with autonomously functioning nodules have toxic adenoma (Plummer disease).
Induced hyperthyroidism by iodine
Transient autoimmune process causing thyroiditis
- Subacute thyroiditis/de Quervain: benign course; viral infections have been associated with the granulomatous giant cell thyroiditis.
- Drug-induced thyroiditis: amiodarone, interferon, interleukin-2, lithium - Postpartum thyroiditis
- Other: functional trophoblastic tumors, pituitary tumors that secrete TSH, and thyrotoxicosis factitia

 Suppressed TSH with normal thyroxine (T4) indicates subclinical hyperthyroidism. The level of TSH is used to determine two grades. TSH levels in grades 1 and 2 range from 0.1-0.39 mU/L for mild suppression and 0.1 mU/L or less for better suppression.

Thyroid storm: uncommon hyperthyroidism; fever, tachycardia, GI symptoms, CNS dysfunction (e.g., coma); up to 50% mortality

Aspects of Geriatrics
Typical symptoms and indications might not be present.
When TSH is less than 0.1 mIU/L, atrial fibrillation is frequent (3)[A].

Child Safety Considerations
Antithyroid medicines are prescribed for newborns and toddlers for 12 to 24 months; radioactive iodine treatment is debatable for patients aged 15 to 18.

pregnant women's issues
Currently, methimazole is recommended in the second and third trimesters of pregnancy, while propylthiouracil is the medication of choice during the first trimester (4)[A]. Use the smallest dose possible to treat. Avoid hypothyroidism brought on by therapy. The use of radioiodine therapy is not advised.

Epidemiology 

1.3% of the populace
Male:female ratio ranges from 7:1 to 10:1.
Predominant age: people over 40 are more likely to have TMNG than those in their 20s or 30s with autoimmune thyroid disease (GD).
Prevalence
In elderly women, the prevalence of hyperthyroidism might rise to 4-5% from 1.3%.

Pathophysiology and Etiology 

Toxic adenoma: point mutation in TSH receptor gene with enhanced hormone production; GD: autoimmune disease; TMNG: 60% TSH receptor gene abnormalities; 40% unknown; Thyroiditis:
- Subacute/de Quervain thyroiditis: granulomatous reaction; genetic predisposition in specific human leukocyte antigens; viruses, including coxsackievirus, adenovirus, echovirus, and influenza virus, have been implicated; self-limited course, 6 to 12 months - Hashitoxicosis: autoimmune destruction of the thyroid; antimicrosomal antibodies present
- Infective: Suppurative
– Thyroiditis brought on by drugs: An autoimmune response and a damaging process are brought on by amiodarone.
An autoimmune thyroiditis is brought on by interleukin-2, interferon, and lithium.
- Postpartum thyroiditis: an autoimmune thyroiditis that can last up to eight weeks and, in 60% of cases, lead to hypothyroidism.
Genetics
In monozygotic twins, the concordance rate for GD is 35%.

Risk factors include: Iodide repletion after iodide deprivation, notably in TMNG; Positive family history, especially in maternal relatives; Other autoimmune illnesses;


Iodine deficiency, Down syndrome, and autoimmune disorders are associated conditions.


History Thyrotoxicosis is a hypermetabolic condition where there is an excess of energy production resulting in increased heat generation, diaphoresis, and even fever.
Thyrotoxicosis has an impact on the following systems:
- Constitutional: drowsiness, lassitude, heightened hunger, and loss of weight
- Neuropsychiatric: emotional instability, agitation, anxiety, psychosis, coma, and poor memory and concentration
- GI: increased hunger and frequent urination
Gynecologic: amenorrhea and oligomenorrhea
Cardiovascular: tachycardia (the most frequent) and chest pain that resembles angina
Aspects of Geriatrics
elderly with apathetic hyperthyroidism

Adult Clinical Examination:
Pretibial myxedema with warm, moist skin (GD alone)
- Exophthalmos and lid lag in the HEENT (head, eye, ear, nose, and throat)
- Endocrine: spider angiomata, goiter, gynecomastia, hyperhidrosis, and heat sensitivity (in males)
Cardiovascular conditions include tachycardia, atrial fibrillation, and cardiomegaly.
Musculoskeletal: fractures
- Neurologic: tremor, weakening of the proximal muscles, lability and anxiety, and rapid deep tendon responses
- Infrequently: localized dermopathy and thyroid acropathy (clubbing).
Young people:
- Acceleration of linear growth
- More frequent ophthalmic abnormalities

Differential Diagnosis: Pheochromocytoma; carcinoid syndrome; Anxiety; Depression; Malignancy; Diabetes Mellitus; Pregnancy; Menopause


Laboratory Results 
95% have increased free T4 and decreased TSH. The bound hormone is represented by total T4 and triiodothyronine (T3), which are impacted by pregnancy and hepatitis.

T3: high, especially in T3 toxicosis or amiodarone-induced thyrotoxicosis (AIT): thyroid-stimulating immunoglobulin or TSH receptor antibody presence is diagnostic of GD.
The free thyroxine index (FTI), which is derived from thyroid hormone-binding ratio and T4 levels, corrects for inaccurate results brought on by pregnancy and estrogens.
TSH that is abnormally normal or increased with a high T4 and is indicative of a pituitary tumor or thyroid hormone resistance
Estrogens, heparin, iodine-containing substances (including amiodarone and contrast agents), phenytoin, salicylates, and steroids (such as androgens, corticosteroids), among others, might affect test findings.
Immunoassays for thyroid hormones, TSH, thyroglobulin, and TSH receptor binding inhibiting antibody might be affected by exogenous biotin supplementation.

Drug warnings: Amiodarone, lithium, and methimazole may cause hyperthyroidism and warfarin resistance, respectively.
Anemia, granulocytosis, lymphocytosis, hypercalcemia, transaminase elevations, and alkaline phosphate elevations are further possible results.

Initial examinations (lab, imaging)

The diagnosis of hyperthyroidism will be made using TSH, free T4, total T4, and T3.

Antibody against the thyrotropin receptor (TRAb)

TSH-R Abs, or antibodies to the TSH receptor: The TSH-binding inhibitor immunoglobulin assay (TBII) is the standard assay.
Both postpartum Graves thyrotoxicosis and neonatal thyrotoxicosis can be predicted with TSH-R Abs.

T4 to T3 ratio When iodine uptake testing is unavailable or contraindicated, the T4-to-T3 ratio may be an effective tool.
2% of people who are thyrotoxic have "T3 toxicosis."
123I or 131I nuclear medicine absorption and scanning For 24-hour radioiodine uptake, the reference range value lies between 5% and 25%.
With TMNG, toxic solitary nodule, and GD, increased thyroid iodine uptake is observed. GD has a diffuse uptake and can have a paradoxical finding of high uptake at 4 to 6 hours but normal uptake at 24 hours due to the quick clearance.
While a single poisonous nodule will appear as a warm or "hot" nodule, TMNG will display a heterogeneous uptake.
Low urine iodine levels are connected to higher uptake in iodine-deficient regions.

Causes of transitory thyrotoxicosis with inadequate iodine uptake include acute thyroiditis, thyrotoxicosis factitia, and iodine intoxication from amiodarone or contrast agents. The patient may become euthyroid or hypothyroid once thyroiditis clears up. - Iodine loading can result in iodine entrapment and reduced iodine uptake (Wolff-Chaikoff effect).
- Thyrotoxicosis factitia: Thyroglobulin levels are high during endogenous production but low during exogenous ingestion.
– Ovarian and metastatic thyroid carcinoma are two more extrathyroidal sources.
- Technetium-99m scintigraphy is debatable because radioactive iodine scanning and it have a 33% discordance rate.
Tests in the Future & Special Considerations
Hospitalize until stable in severe situations, such as thyroid storm, especially if you are over 60 because atrial fibrillation is a concern.
Other/Diagnostic Procedures
Increased diffuse vascularity will be visible on a neck ultrasonography in GD.
Test Interpretation: Hyperplasia in the GD; development of toxic nodules.

Management 

 Patients with moderate hyperthyroidism (TSH >0.1 or no symptoms), especially those who are young and have a low risk of consequences (atrial fibrillation, osteoporosis), may benefit from observation.
Patients with thyroiditis should not take antithyroid medication. NSAIDs and beta-blockers are used as supportive therapies for subacute thyroiditis. For two to three weeks, steroids can be taken (4). Antithyroid medication, radioactive iodine therapy (RAIT), or thyroid surgery are all options for treating GD or TMNG.
The most popular definitive treatment for GD and TMNG in the United States is RAIT.
To prevent the thyrotoxicosis following RAIT from getting worse, pretreatment with antithyroid medications is preferred. Because it reduces relapse, methimazole is favored over propylthiouracil as a pretreatment; nevertheless, it is held 3 to 5 days prior to therapy.

Antithyroid drugs are kept up after ablation because most patients develop hypothyroidism 2 to 3 months following RAIT.
Glucocorticoids lessen the conversion of active T4 to the more active T3, which is a side effect. Prednisone is used before and after RAIT in patients with Graves ophthalmopathy to stop the condition from getting worse.

Prior to prescribing RAIT for GD, a 12- to 18-month trial of antithyroid drugs may be taken into consideration given the possibility of remission.
The preferred treatment for TMNG is RAIT. Antithyroid medical therapy has a significant rate of recurrence, according to research. Surgery is only considered in unique circumstances.
Treatment for AIT type I involves antithyroid medications and beta-blockers. The final option is thyroidectomy. AIT type II uses glucocorticoids but is self-limited.

Blockers can help people with rapid sinus rhythm manage their palpitations and lower their heart rates.

First Line of Medicine
Antithyroid medications: Thioamides methimazole and propylthiouracil prevent the oxidation, organification, and iodotyrosine coupling of iodine. Propylthiouracil has the ability to prevent peripheral T4 to active T3 conversion. Both can be used as the first line of defense against GD and before RAIT or surgery.

Treatment lasted 12 to 18 months; 50% to 60% of patients relapsed after discontinuing; continued treatment did not improve the remission rate after 18 months. Hepatitis (0.1–0.2%), vasculitis, and agranulocytosis are the most severe adverse effects; baseline CBC is advised:
- Methimazole (preferred): Adults: 10 to 15 mg every 12 to 24 hours; children aged 6 to 10 years: 0.4 mg/kg/day PO once daily.
- Propylthiouracil: adults (recommended in thyroid storm and the first trimester of pregnancy): 100 to 150 mg PO every eight hours; during pregnancy, do not take more than 200 mg per day.
-Adrenergic blocker: Propranolol suppresses T3 activation by up to 30% at high doses (>160 mg/day). Patients with sinus tachycardia can benefit from the use of atenolol, metoprolol, and nadolol, which can also be helpful in reducing palpitations and lowering heart rate.

 Glucocorticoids: lessen the process by which active T4 is converted to the more active T3.
Cholestyramine is an anion exchange resin that reduces the reabsorption of thyroid hormone in the enterohepatic circulation. The recommended dosage is 4 g QID.
Additional agents
Lithium: Use is constrained by toxicity; it inhibits the release of thyroid hormones and the iodotyrosine coupling.
- The Jod-Basedow effect; Lugol solution or saturated solution of potassium iodide (SSKI); suppresses hormone release from the gland but should be given at least an hour after thioamide was given.
– RAIT.


Referral 

Send Graves ophthalmopathy patients to a qualified ophthalmologist.


Surgical Techniques 

Only during the second trimester of pregnancy is a thyroidectomy allowed for compressive symptoms, masses, and thyroid cancer.

Follow Up Patients with GD who smoke should stop because it's a risk factor for ophthalmopathy, especially after RAIT Patient Monitoring.
While taking thioamides, repeat thyroid tests every three months (q3mo), CBCs, and liver function tests (LFTs); keep taking thioamides for 12 to 18 months.
If the patient is thyroidally euthyroid following RAIT, thyroid function tests should be performed at 6 weeks, 12 weeks, 6 months, and annually after that. TSH levels should be monitored alongside T3 and T4 levels.
DIET
enough calories to stop weight loss

Good prognosis in the event of early detection and treatment

Complications include: Graves ophthalmopathy, worsening heart failure if cardiac condition, atrial fibrillation, muscle wasting, proximal muscle weakness, increased risk of cerebrovascular accident (CVA), and cardiovascular mortality. Surgery-related complications include hypoparathyroidism, recurrent laryngeal nerve damage, and hypothyroidism.

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