Thyroid Disorders

Term

Definition

Thyroid hormone function in children

Critical for normal growth and development.

Thyroid hormone function in adults

Maintains metabolic stability.

HPT Axis

Hypothalamic-Pituitary-Thyroid Axis; self-regulatory circuit that maintains thyroid homeostasis. Hypothalamus releases TRH, pituitary releases TSH, thyroid releases T3/T4.

TSH

Thyroid-stimulating hormone (thyrotropin); produced by anterior pituitary; stimulates thyroid gland to produce T3 and T4.

TRH

Thyrotropin-releasing hormone; produced by hypothalamus; stimulates pituitary to release TSH.

Thyroglobulin (TG)

Precursor protein for thyroid hormone; contains tyrosine amino acids; produced by thyrocytes.

Thyroid Peroxidase (TPO)

Enzyme that converts iodide to iodine (oxidation), places iodine into tyrosine (iodination/organification), and aids coupling of MIT and DIT.

Iodination

Process of placing iodine into tyrosine using TPO.

MIT

Monoiodotyrosine; formed when one iodine is placed on tyrosine.

DIT

Diiodotyrosine; formed when two iodine units are placed on tyrosine.

Coupling

Process of combining MIT and DIT to form T3 and T4; uses TPO enzyme.

T3 (Triiodothyronine)

Formed by one MIT + one DIT. Main active thyroid hormone.

T4 (Thyroxine/Tetraiodothyronine)

Formed by DIT + DIT. Main product secreted by thyroid gland (100-125 nmol daily). Half-life 7-10 days; converted peripherally to T3.

TBG

Thyroxine-Binding Globulin; protein that binds majority of T3 and T4 in blood.

Pendrin

Transporter that moves iodide from follicular cells into colloid.

Primary hypothyroidism

Thyroid gland failure; TSH elevated, free T4/T3 low. Most common (95% of hypothyroidism cases). Caused by autoimmune thyroiditis (Hashimoto's).

Secondary hypothyroidism

Pituitary failure → decreased TSH → decreased T4/T3. Rare; affects sexes equally. Causes: pituitary tumors, Sheehan syndrome, radiation, trauma.

Tertiary hypothyroidism

Hypothalamic failure → decreased TRH → decreased TSH → decreased T4/T3. Causes: cranial irradiation, trauma, infiltrative/neoplastic diseases.

Hashimoto's thyroiditis

Autoimmune thyroiditis; most common cause of spontaneous hypothyroidism in adults. Can present with goiter (mild disease) or gland atrophy (severe deficiency).

Hypothyroidism prevalence

Up to 5% of general population; another estimated 5% undiagnosed. Women 5-8x more likely than men.

Hypothyroidism risk factors

Autoimmune conditions (Type 1 diabetes, RA, SLE), female sex, age >60, family history, iodine imbalance, previous neck radiation.

Hypothyroidism clinical manifestations

Slowing of physical/mental activity, bradycardia, cold/dry skin, periorbital puffiness, hoarse voice, proximal muscle weakness, slow relaxing DTRs, macrocytic anemia, effusions (pericardial/pleural/peritoneal).

Myxedema

Advanced hypothyroidism with swelling of skin and subcutaneous tissues.

Myxedema coma

Rare but fatal complication of severe untreated hypothyroidism. Precipitated by hypothermia, stress, infection, trauma, beta-blockers, narcotics, anesthetics. Medical emergency.

Myxedema coma treatment

IV bolus levothyroxine 300-500 mcg (or IV T3 or combination). IV hydrocortisone 100 mg q8h until adrenal suppression ruled out. Supportive therapy for ventilation, BP, temperature, glucose.

Levothyroxine (T4)

Drug of choice for hypothyroidism replacement therapy. Initial dose 1.6 mcg/kg/day (reduced in elderly and atrial fibrillation patients).

Levothyroxine administration

Take 30-45 min before breakfast or at least 3 hours post-meal at bedtime for enhanced absorption.

Levothyroxine dose adjustment

TSH checked 6 weeks after dose change. Median maintenance dose 125 mcg daily (range 100-200 mcg). During pregnancy, increase dose by 25-50%.

Levothyroxine absorption inhibitors

Calcium, magnesium, PPIs, sucralfate, cimetidine negatively impact absorption.

Levothyroxine adverse effects

Overtreatment: atrial fibrillation, osteoporosis. Undertreatment: adverse lipid profile, progression of CVD.

Levothyroxine monitoring

TSH 4-8 weeks after initiation, dose changes, or preparation change until euthyroid; then every 6-12 months.

Central hypothyroidism monitoring

Based on free T4 rather than TSH.

Hyperthyroidism

Production of excessive amounts of thyroid hormones by the thyroid gland.

Thyrotoxicosis

Clinical syndrome associated with prolonged exposure to elevated thyroid hormone levels.

Most common cause of thyrotoxicosis

Graves' disease (approximately 95% of cases).

Graves' disease

Autoimmune condition from abnormal IgG immunoglobulin (TSAb/TRAB) that occupies TSH receptor, mimicking TSH effect → cell division and thyroid hormone secretion.

Graves' disease demographics

90% are young women, often with family history. May have congestive ophthalmopathy (lid retraction, proptosis, periorbital edema).

Graves' disease in pregnancy

Maternal TRABs cross placenta → transient neonatal thyrotoxicosis.

Toxic multinodular goiter

Common cause of hyperthyroidism in older demographic.

Jod-Basedow phenomenon

Iodine-induced hyperthyroidism caused by amiodarone or other iodine-containing medications.

Postpartum thyroiditis

Occurs within 6 months after delivery. Self-limiting. Risk factors: antithyroid antibodies pre-pregnancy, prior thyroid problems, Type 1 diabetes.

Subacute (De Quervain) thyroiditis

Self-limiting; occurs after viral infection (mumps, flu, common cold). Manage with symptomatic therapy only.

Factitious thyroiditis (thyrotoxicosis factitia)

Hyperthyroidism from inappropriate/excessive use of pharmaceutical thyroid hormone.

Hyperthyroidism lab findings

Low TSH, high free T3, high free T4.

Symptomatic therapy for hyperthyroidism

Beta-blockers (propranolol, atenolol, metoprolol) for palpitations, anxiety, tremors. Second-line: verapamil for beta-blocker intolerance.

Definitive therapy options for hyperthyroidism

RAI (radioactive iodine), thionamides (methimazole, PTU), subtotal thyroidectomy. All predispose to potential long-term hypothyroidism.

RAI (Radioactive Iodine)

Treatment of choice for Graves disease (high efficacy). Contraindicated in pregnancy/breastfeeding. Discontinue thionamides ~1 week prior.

Methimazole vs PTU

Equally effective but methimazole preferred due to better safety profile. Exception: pregnancy — PTU preferred (methimazole associated with congenital defects).

PTU (Propylthiouracil)

Treatment of choice for gestational hyperthyroidism. Also preferred in thyroid storm due to inhibition of peripheral T4 to T3 conversion.

Methimazole dosing (mild)

15 mg/day PO divided q8hr initially.

Methimazole dosing (moderate)

30-40 mg/day PO divided q8hr initially.

Methimazole dosing (severe)

60 mg/day PO divided q8hr initially.

Methimazole maintenance

5-30 mg/day PO divided q8hr.

PTU dosing for hyperthyroidism

300-450 mg/day PO divided q8hr initially (may need up to 600-900 mg/day). Maintenance: 100-150 mg/day divided q8hr.

PTU dosing for thyrotoxic crisis

Initial 200-300 mg PO q4-6hr on Day 1, then reduce gradually. Maintenance: 100-150 mg/day divided q8-12hr.

Thionamide response timeline

Response seen in 4-6 weeks; maximal response in 4-6 months. Treatment continues 1-2 years.

Agranulocytosis

Rare but severe adverse effect of both methimazole and PTU.

Subtotal thyroidectomy preparation

Pretreat with methimazole to achieve euthyroid state; add supersaturated potassium iodide (16 drops/day Lugol's 5% solution) ~2 weeks before surgery.

Subtotal thyroidectomy complications

Hypothyroidism, hypoparathyroidism, vocal cord paralysis.

Graves' ophthalmopathy treatment

Mild: artificial tears (day) and lubricating gels (night). Severe: corticosteroids (prednisolone). Teprotumumab (Tepezza) FDA-approved.

Thyroid storm

Life-threatening complication of untreated/unmanaged hyperthyroidism. Symptoms: tachycardia, increased GI motility, diaphoresis, anxiety, fever.

Thyroid storm management

PTU (inhibits peripheral T4→T3 conversion) plus beta-blockers.

Iodized salt

Primary therapy for goiter due to iodine deficiency in developing countries.

Thyroid nodules prevalence

Seen in 4-7% of adults; may be malignant or autonomously secrete thyroid hormones.

Sheehan syndrome

Postpartum pituitary necrosis causing secondary hypothyroidism.

Goitrogens

Substances that cause goiter; maternal ingestion during fetal development can cause cretinism.

Sick euthyroid syndrome

Non-specific consequence of systemic illness causing decreased T3 and T4; requires specialist assessment.

Levothyroxine dosing in elderly/reduced cardiac function

Reduced dose; start low and go slow with incremental changes of 12.5-25 mcg every 4-8 weeks.

Carbimazole dosing (adults)

20-60 mg/day in 2-3 divided doses.

Carbimazole dosing (children)

15 mg/day once daily or 2-3 divided doses.

TSH as first-line test

Caveat: can result in delayed diagnosis of secondary/tertiary hypothyroidism (suspect with low free T4 and low TSH).

Iodine ingestion and hypothyroidism

In sensitive persons (autoimmune thyroiditis), iodide blocks thyroid hormone synthesis → increased TSH and thyroid enlargement.

Medications causing hypothyroidism

Lithium, amiodarone, interferon-α, interleukin-2, tyrosine kinase inhibitors, sulphonylureas, rifampicin.

Medications causing iatrogenic Cushing syndrome (thyroid unrelated but mentioned)

Progestins (medroxyprogesterone acetate, megestrol acetate).

Precipitation of hypoadrenal crisis

Before starting T4 replacement, rule out glucocorticoid deficiency; if doubt, give hydrocortisone until cortisol deficiency excluded.

TRABs

Thyroid receptor antibodies; abnormal IgG in Graves' disease that stimulate TSH receptor.

TSAbs

Thyroid stimulating antibodies; stimulatory immunoglobulins in Graves' disease.

Pharmacist role in thyroid disorders

Not explicitly detailed but implied: medication counseling, monitoring, adherence, drug interactions, special populations.

Iodine to iodide conversion

Iodide (absorbed) → iodine (for thyroid hormone synthesis) via TPO oxidation.