Hypothyroidism mechanisms & Hashimoto's thyroiditis

• The case involves a middle-aged woman with fatigue and general weakness.

Case Resolution and Review

• The patient is diagnosed with Hashimoto's thyroiditis, a chronic autoimmune disease.
• This disease progressively destroys thyroid epithelial cells (follicular cells) through apoptosis.
• The destruction of follicular cells leads to decreased production of triiodothyronine (T3) and thyroxine (T4).
• Patients experience symptoms of hypothyroidism as a result.

Patient Case Details

• Mrs. Potter reports fatigue, general weakness, and frequent muscle cramping over several months.
• Other symptoms include constipation, weight gain, and feeling cold, consistent with hypothyroidism.
• Thyroid hormone (TH) enhances muscle contractility, regeneration, and metabolism.
• Hypothyroidism delays muscle contraction and relaxation, causing pain and cramps.
• Constipation is common in hypothyroidism because TH increases peristalsis in the GI tract and enhances digestive enzyme secretion.
• Low thyroid hormone levels slow metabolism and lower the basal metabolic rate (BMR), leading to fatigue, weight gain, and decreased thermogenesis (feeling cold).
• Patient has a history of rheumatoid arthritis, and her husband reports increased forgetfulness and depression.
• Rheumatoid arthritis suggests the hypothyroidism is due to Hashimoto's thyroiditis, as rheumatoid arthritis is an autoimmune disease.
• Rheumatoid arthritis and other autoimmune diseases are risk factors for Hashimoto's thyroiditis.
• Iodine deficiency is likely not a factor due to her "well-balanced diet."
• Memory loss and depression are frequently reported in Hashimoto's thyroiditis (over 25% of cases).
• Thyroid hormone (TH) deficiency reduces synaptic transmission and plasticity in the CA1 region of the hippocampus, potentially causing memory impairment.

Physical Examination Findings

• Dry, coarse skin on arms
• Bald spot
• Thinning eyebrows
• Delayed deep tendon reflex
• Hypothyroid patients typically have dry, cold, yellowish, and thickened skin.
• Dermal accumulation of hydrophilic mucoproteins (like hyaluronic acid) causes these changes by binding water, leading to myxedema.
• The effects are due to either direct effects of TH or the autoimmune response.
• Human hair follicles are direct targets of TH, and hypothyroidism can result in hair loss and thinning. The delayed deep tendon reflex relates to thyroid hormone effects on muscle function.
• Neck examination reveals fullness, and palpation indicates a nodule on the thyroid gland.
• Over 90% of thyroid nodules are benign, but evaluation is recommended to rule out cancer.
• Malignant nodules usually indicate papillary thyroid carcinoma, the most common type of thyroid cancer.
• The cause of benign nodules is unknown, but Hashimoto's thyroiditis increases the risk of developing thyroid nodules.

Vital Signs and Blood Tests

• Low heart rate (bradycardia)
• High diastolic blood pressure
• The heart's primary pacemaker depends on TH.
• TH upregulates ẞ1 adrenergic receptors, initiating sympathetic nervous system signaling in the heart, which contributes to decreased heart rate in hypothyroidism.
• Endothelial dysfunction and impaired vascular smooth muscle relaxation lead to increased systemic vascular resistance, causing diastolic hypertension in ~25% of patients.
• Blood tests show: Low erythrocyte count, high total cholesterol, high triglyceride level, and high LDL cholesterol level.
• Hypothyroidism can result in decreased RBC count, erythrocyte size (MCV), and hemoglobin concentration.

Thyroid Hormone Regulation

• Low T3 and T4 levels trigger the hypothalamus to release thyroid releasing hormone (TRH).
• TRH acts on the anterior pituitary gland, stimulating the release of thyroid stimulating hormone (TSH).
• The patient's serum TSH/thyrotropin level is elevated.
• TSH acts on the thyroid gland to produce T3 and T4.
• Elevated levels of anti-thyroperoxidase (TPO) antibody confirm Hashimoto's thyroiditis, a chronic autoimmune inflammation of the thyroid gland.
• TPO catalyzes the iodination of tyrosine residues and oxidative coupling of iodotyrosine residues on the thyroglobulin (TG) molecule.
• Antibodies against TPO target the follicular cells of the thyroid, leading to destruction.
• White blood cells, including B lymphocytes, gather in the thyroid, and plasma cells make the antibodies that initiate the autoimmune process.

Thyroid Biopsy and Treatment

• A core biopsy reveals a benign nodule and an abnormal thyroid.
• There is loss of thyroid follicles, lymphocytic infiltration, and secondary lymphatic nodules, typical of Hashimoto's thyroiditis.
• There is extensive infiltration of the parenchyma by a mononuclear inflammatory infiltrate (small lymphocytes, plasma cells) and secondary lymphatic nodules with germinal centers.
• Mrs. Potter is treated with levothyroxine, a synthetic form of thyroxine (T4).
• After eight weeks, blood test values move closer to normal ranges, but T3 and T4 levels are still slightly lower than normal.
• Titration of the levothyroxine dose brings her values within normal range.
• Mrs. Potter's hypothyroidism is controlled, and she feels like her old self again; levels should be monitored annually.

Explore the mechanisms behind hypothyroidism, its association with Hashimoto's thyroiditis, and related symptoms. The question set covers cognitive dysfunction, skin changes, hair follicle targeting, delayed reflexes, thyroid cancer risks, bradycardia, adrenergic receptors, and diastolic hypertension.