Thyreotoxicosis

• The hypothalamic-pituitary-thyroid (HPT) axis operates on a negative feedback loop
• The hypothalamus releases thyrotropin-releasing hormone (TRH) when it detects low thyroid hormone levels
• TRH travels through the hypophyseal portal system to the anterior pituitary
• The anterior pituitary then releases thyroid-stimulating hormone (TSH), also known as thyrotropin
• TSH stimulates the thyroid gland to release thyroid hormones

Thyroid Gland

• Thyroid disorders represent the most common endocrinopathies
• The thyroid comprises thousands of follicles lined with follicular cells
• Follicular cells convert thyroglobulin into T3 or T4
• Once released, these hormones bind to plasma proteins in the blood, leaving only a small fraction unbound
• Inside cells, T4 converts to T3, which speeds up the cell's basal metabolic rate
• As a result, cells produce more proteins and burn more energy in the form of sugars and fats, increasing cardiac output
• Thyroid hormone also stimulates bone resorption and activates the sympathetic nervous system
• Gluconeogenesis, fatty acid synthesis (B-oxidation) in the liver, and lipolysis in adipose tissue are subsequently activated

Hyperthyroidism

• Hyperthyroidism involves an excess of thyroid hormones, leading to a hypermetabolic state
• Primary hyperthyroidism stems from issues with the thyroid gland itself producing excess hormones
• Secondary hyperthyroidism results from problems with the pituitary gland or hypothalamus, causing higher TSH production

Primary Hyperthyroidism

• Grave’s disease represents the most common cause
• Grave's disease is an autoimmune disorder where B-cells produce antibodies against thyroid proteins
• Thyroid-stimulating immunoglobulins bind to TSH receptors on follicular cells that mimic TSH
• This results in growth of the thyroid gland and production of excess thyroid hormone
• Toxic nodular goiter (toxic adenoma) occurs when one or more follicles generate excessive thyroid hormones
• Hyperfunctioning thyroid adenoma involves follicular cells growing uncontrollably, forming a benign tumor and making excess thyroid hormones
• Jöd-Basedow syndrome (iodine-induced thyrotoxicosis) can develop after an iodine-deficient person receives a large dose of iodine
• Thyroid inflammation can cause a large release of pre-formed thyroid hormones
• Neonatal hyperthyroidism occurs when newborns of mothers with Grave’s disease produce excess thyroid hormone due to thyroid-stimulating immunoglobulin crossing the placenta

Other Causes of Hyperthyroidism

• Follicular carcinoma
• Thyrotoxicosis factitia
• Paraneoplastic hyperthyroidism (embryonal carcinoma of testes, mole hydatidosa = molar pregnancy)

Secondary Hyperthyroidism

• Pituitary thyrotropic adenoma causes higher TSH production when thyroid gland is normal
• The thyroid gland generates a lot of thyroid hormone in response to a TSH-secreting tumor in the anterior pituitary

Symptoms of Hyperthyroidism

• Cardiological signs include tachycardia, hypertension, palpitations, extrasystoles, a. fib., and thyrotoxic cardiomyopathy
• Skin symptoms include moist, sweaty skin, radiant palms, and fine hair, and head hair loss
• Diarrhea
• Weight loss despite good appetite due to higher basal metabolic rate, although 10% of patients gain weight
• Heat intolerance because the body if producing more heat
• Menstrual irregularities may also occur
• Characteristics of Grave’s disease include
• Tachycardia, goiter, exophthalmos, a diffusely enlarged soft thyroid gland that can pulsate, and a tactile vortex may be present.
• Endocrine orbitopathy manifests as exophthalmos along with Moebius, Graefe, and Dalrymple signs, and lagophthalmos
• Long-term hyperthyroidism can lead to congestive heart failure and osteoporosis

Diagnosis of Hyperthyroidism

• Confirmed by thyroid function tests measuring TSH activity and free T4
• Increased free T4 with decreased TSH indicates primary hyperthyroidism.
• Increased free T4 with increased (or normal) TSH indicates secondary hyperthyroidism and thyrotropic pituitary adenoma
• Specific antibodies, such as anti-TSH-receptor antibodies in Grave’s disease, or calcitonin and cholesterol levels can be measured
• Ultrasound and aspiration biopsy with a thin needle with cytological examination is the basic diagnostic procedure
• Scintigraphy and CT examination are performed if malignancy or toxic adenoma are suspected

Treatment of Hyperthyroidism

• Treatment depends on the cause, but generally includes drugs like beta blockers to treat immediate symptoms
• Anti-thyroid drugs block thyroid hormone production and release, eg, propul-thio-uracil
• Radioiodine therapy destroys the thyroid partially or completely, followed by replacement hormone therapy
• In a few cases, the thyroid is removed with surgery (subtotal thyroidectomy)

Thyroid Storm

• Thyroid storm involves increased activity of thyroid hormones stemming from untreated or poorly treated hyperthyroidism
• Associated factors: infection, injury, amiodarone use, interruption of thyrostatic treatment, and iodine preparations exposure.
• Escalated hyperthyroidism symptoms can endanger the patient’s life, with mortality rates between 30-50%
• Common symptoms include fever, heat intolerance, sweating, tachycardia, atrial fibrillation, palpitations, nausea, diarrhea, abdominal pain, and neuropsychological changes (agitation, delirium, tremor, or convulsions)
• Diagnosis involves characteristic findings in laboratory parameters which are increased of free T4 and T3 values, and a decrease in TSH

Treatment of Thyroid Storm

• Administer thyrostatics (propylthiouracil, thiamazole) to inhibit the increased synthesis and release of thyroid hormones, potassium iodide (slows the release of thyroid hormones), hydrocortisone
• Beta blockers for cardiovascular problems, paracetamol or physical cooling to reduce temperature, oxygen therapy, and rehydration
• Total thyroidectomy is an important treatment option for difficult-to-manage thyrotoxic crisis
• Osmosis: The thyroid storm is a life-threatening complication of hyperthyroidism where the body goes into a state of severe hypermetabolism
• It can develop when someone with hyperthyroidism stops their treatment, develops an infection, or has surgery
• All of the normal symptoms of hyperthyroidism become exaggerates, for example heat intolerance turns to high fever and rapid heart rate turns into cardiac arrhythmia

The hypothalamic-pituitary-thyroid (HPT) axis operates on a negative feedback loop. The hypothalamus releases thyrotropin-releasing hormone (TRH) when it detects low thyroid hormone levels, stimulating the anterior pituitary to release thyroid-stimulating hormone (TSH). TSH stimulates the thyroid gland to release thyroid hormones.