Thyroid Disorders and Treatments Quiz

Thyroid Gland

• The thyroid gland is located in the neck, and has two lobes connected by an isthmus.
• Sometimes a pyramidal lobe is present above the isthmus.
• The thyroid is supplied by superior and inferior thyroid arteries.
• The superior thyroid receives blood from the first branch of the external carotid artery.
• The inferior thyroid receives blood from the thyrocervical trunk, an offshoot of the subclavian artery.
• Thyroid tissue originates from the floor of the pharynx, composed of epithelial cells.
• The thyroid develops initially in a duct which connects to the tongue in a child.
• This duct disappears during development.
• Remnants of this duct exist in a child/adult in a structure called the thyroglossal duct.
• There are remnants of the duct such as foramen cecum in the tongue and pyramidal lobes of the thyroid.
• A thyroglossal duct cyst is a mass that may form in the midline of the neck because of a persistent remnant of the thyroglossal duct.
• Ectopic thyroid tissue can develop outside of the main thyroid gland, often found in the base of the tongue.
• Thyroid tissue contains follicles filled with colloid, a protein material.
• Follicular cells line these follicles.
• Thyroid hormones, T3 and T4, are synthesized from tyrosine and iodine.
• Iodized salt contains a small amount of iodine and was added to salt in the US in 1924.
• Thyroid hormones are synthesized from tyrosine and iodine forming T3 and T4.
• Thyroglobulin is a large protein containing numerous tyrosine molecules and is produced by thyroid follicular cells.
• Iodine, which is present in the diet as an iodide salt, is taken up by follicular cells to form thyroid hormones.
• Iodide is oxidized into I2 and then added to organic/carbon structures.
• Thyroid peroxidase (TPO) catalyzes the oxidation of iodine.
• TPO also couples MIT/DIT into T3/T4.
• Two hormones: T3 and T4 are synthesized from tyrosine and iodine.
• T4 is a prohormone and 5' deiodinase converts T4 to T3 in peripheral tissues.
• T4 is the primary thyroid hormone secreted by the thyroid which is converted to T3 which is more potent.

Thyroid Hormones

• Most thyroid hormone is formed as T4.
• T3 is more potent than T4 and acts as a prohormone.
• T3 and T4 affect metabolism.

Thyroid Histology

• Thyroid glands contain follicles that are filled with colloid.
• A single layer of follicular cells lines these follicles.
• Follicular cells synthesize hormones.

Thyroid Embryology

• The thyroid develops from pharyngeal epithelial cells.
• Initially, the thyroid is connected to the tongue by a duct.
• This connection dissipates later in development.
• Remnant tissue from this duct may remain.

Thyroid Disorders

• Thyroid disorders include hyperthyroidism, hypothyroidism, and thyroiditis.

Hypothyroidism

• Metabolism slows down.
• Symptoms include lethargy, fatigue, cold intolerance, weight gain, constipation, hyporeflexia, dry/cool skin, coarse/brittle hair, and bradycardia.
• A feature of hypothyroidism is elevated cholesterol.

Hyperlipidemia

• Elevated cholesterol is a feature of hypothyroidism (↑ total cholesterol and LDL).
• ↓ LDL receptor density is a mechanism.
• T3 upregulates LDL receptor gene activation.

Myxedema

• Myxedema is non-pitting edema.
• Hyaluronic acid deposits in the dermis causing swelling.
• Seen with Grave's disease (hyperthyroidism).
• Myxedema coma is from hypothyroidism.

Hypothyroid Myopathy

• Muscles symptoms (weakness, cramps, myalgias) with elevated serum creatine kinase are common in hypothyroidism..
• Symptoms are often present in patients with hypothyroidism.

Hyponatremia

• Hypothyroidism can cause hyponatremia (low sodium levels).
• This can occur due to high levels of ADH.
• This can cause confusion

Thyroid Replacement

• Levothyroxine (synthetic T4) is commonly prescribed for replacement therapy.
• Liothyronine (synthetic T3), which is absorbed rapidly from the intestines, is sometimes used.
• Levothyroxine is preferred due to its slower absorption and prolonged activity.
• Treatment can cause mild symptoms like hyperthyroidism (tachycardia, tremor), so the dosage is adjusted until TSH is normal.

Hyperthyroidism

• Metabolism speeds up.
• Symptoms include hyperactivity, heat intolerance, weight loss with increased appetite, diarrhea, hyperreflexia, warm/moist skin, fine hair, and tachycardia.

Thyroid Storm

• A life-threatening hyperthyroidism.
• Often precipitated by an acute event like infection, surgery, or trauma to a patient with existing hyperthyroidism.
• High catecholamine levels, fever, delirium, tachycardia, hyperglycemia, and hypercalcemia are potential complications.

Goiter

• An enlarged thyroid gland.
• Often accompanied by high TSH levels but inadequate T3/T4 production.
• Grave's thyroid stimulating antibodies can cause goiters.

Lab Findings

• TSH is the best initial test for evaluating thyroid function.
• In hypothyroidism, TSH is typically elevated, with low levels of T3 and T4.
• In hyperthyroidism, TSH is typically suppressed, with high levels of T3 and T4.
• Central hyper/hypo thyroid disease is often marked by low TSH and low T3/T4 or high TSH and high T3/T4 levels.
• Disorders in the pituitary and hypothalamus are often the cause.

Reverse T3

• Is an isomer of T3 that is derived from T4.
• Euthyroid sick syndrome, a condition that occurs in critically ill patients, is marked by low T3/T4 and elevated rT3.

Hyperthyroidism Causes

• Grave's disease, toxic multinodular goiter, amiodarone, iodine load, and early thyroiditis.

Grave's Disease

• Grave's is an autoimmune disease.
• Thyroid stimulating antibodies are produced.
• Symptoms of hyperthyroidism occur.
• Exophthalmos (bulging eyes) and pretibial myxedema can occur with Grave's disease.
• The inflammatory mechanism involves T-cell lymphocytes activating fibroblasts, specifically fibroblasts containing TSH receptors.
• Stimulation leads to glycosaminoglycan secretion, drawing in water, resulting in swelling.

Grave's Disease Diagnosis/Treatment

• Diagnosis often involves thyroid labs plus exophthalmos.
• TSH receptor antibodies/thyroid stimulating immunoglobulins can also be measured.
• Treatment includes beta blockers, thionamides, radioactive iodine ablation or surgery.

Thionamides

• Thionamides such as methimazole and propylthiouracil are used to treat hyperthyroidism.
• Inhibiting TPO to stop thyroxine synthesis is the mechanism of action.
• Some potential side effects include skin rash and agranulocytosis (rare dangerous drop in WBC).

Thyroid Cancer

• Common thyroid cancers include papillary, follicular, medullary, and anaplastic.

Papillary Carcinoma

• Often presents as a nodule; may be seen in prior radiation exposure.
• Psammoma bodies, nuclear grooves, and "Orphan Annie's eyes" are key pathology findings with diagnosis made by nuclear findings.

Follicular Carcinoma

• Similar to follicular adenomas.
• Breaks through the fibrous capsule; FNA cannot distinguish between it and adenoma over time.

Medullary Carcinoma

• Cancer of parafollicular cells.
• Produces calcitonin.

MEN Syndromes

• MEN syndromes are genetic syndromes causing multiple endocrine tumors.
• MEN 2A/2B are associated with medullary thyroid carcinoma.
• RET oncogene mutations cause MEN.

Anaplastic Carcinoma

• Highly malignant; often occurs in elderly patients.
• Characterized by undifferentiated cells, lack of usual thyroid features like papilla, follicles, or amyloid, and rapid invasion leading to a poor prognosis.

Adrenal Glands

• Located above the kidneys.
• They have a cortex and medulla.

Cortex

• Three groups of hormones.
• Mineralocorticoids (aldosterone),
• Glucocorticoids (cortisol),
• Androgens (testosterone).

Medulla

• Epinephrine, and norepinephrine.

Signal Transmission

• Catecholamines released from the neural crest cells.
• Neurotransmitters such as acetylcholine, and norepinephrine/epinephrine mediate parasympathetic/sympathetic responses in the body.

Mineralocorticoids

• Aldosterone is the most important mineralocorticoid.
• Aldosterone affects kidney function.
• Its release is controlled by the renin-angiotensin-aldosterone (RAA) system.
• Na+/water reabsorption and K+/H+ excretion is its function.

Collecting Duct

• Principal and intercalated cells are crucial in the collecting duct, regulating water and electrolyte balance with the help of aldosterone.

Adrenal Androgens

• Small contribution in males.
• 50% relevance in female adrenal hyperplasia.
• Over/under production causes abnormal sexual development.
• ACTH stimulates production similarly to cortisol.

Cortisol

• A major glucocorticoid.
• Synthesized by adrenal cortex.
• Binds to intracellular receptors and regulates gene transcription.

Pituitary-Adrenal Axis

• Hypothalamus releases hormones to control the release of cortisol via the pituitary gland.
• Corticotropin-releasing hormone (CRH) initiates this process to stimulate ACTH secretion in the anterior pituitary.

Circadian Rhythms

• Serum cortisol is highest early in the morning (about 6AM).
• Cortisol levels are lowest one hour after sleep onset.

Cortisol Binding Globulin

• Cortisol is poorly soluble in plasma.
• Bound to CBG, accounts for over 90%.
• Levels increase with estrogen.

Cortisol Effects

• Blood pressure maintenance.
• Effects on vascular smooth muscle.
• Increases vascular sensitivity (alpha1) to norepinephrine/epinephrine.
• NO mediated vasodilation.
• Cortisol affects blood pressure with hypertension in Cushing's disease and hypotension in adrenal insufficiency.
• Immune system suppression includes sequestering lymphocytes in the spleen, reducing T/B cell levels in blood, blocking neutrophil migration, increasing peripheral neutrophil count, and decreasing eosinophil counts.
• Cortisol inactivates NF-kB, key inflammatory transcription factor, mediating the inflammatory response, and controlling the inflammatory mediators (e.g., COX-2, PLA2, Lipoxygenase).

Corticosteroid Drugs

• Examples of synthetic glucocorticoids for use in disease.

Cortisol Effects in Metabolism

• Increased glucose production by the liver (gluconeogenesis), less glucose taken up by muscle and fat, resulting in increased serum glucose.
• Increased liver glycogen storage and glycogen synthase synthesis.

Cortisol Effects on Lipid Metabolism

• Increased lipolysis in adipocytes.
• Increased free fatty acids.
• Increased total cholesterol and triglycerides.
• Stimulates adipocyte growth (fat deposition).

Cortisol Effects

• Glucagon and epinephrine effects are enhanced.
• Long-term steroid use causes diabetes.

Cortisol Effects on Skin

• Muscle atrophy and decreased epidermal cell division, resulting in thinning of skin, easy bruising, and reduced collagen formation, creating stretch marks.

Cortisol Effects on Bones

• Inhibits osteoblast activity, which contributes to osteopenia/osteoporosis.

Zones of the Adrenal Glands

• Adrenal glands have distinct zones (glomerulosa, fasciculata, reticularis) with each producing specific hormones:
  • Zona glomerulosa: Primarily mineralocorticoids (aldosterone).
  • Zona fasciculata: Primarily glucocorticoids (cortisol).
  • Zona reticularis: Primarily androgens.
  • Medulla: Primarily catecholamines (epinephrine, norepinephrine).

Zona Glomerulosa

• Details of the synthesis of aldosterone.
• Steps from cholesterol to aldosterone synthesis.
• ACTH stimulation of aldosterone synthesis pathway.

Zona Fasciculata

• Steps in cortisol synthesis.
• Pathways from cholesterol to cortisol synthesis.

Zona Reticularis

• Steps in the synthesis of adrenal androgens and their pathways.

Ketoconazole

• Antifungal that blocks ergosterol synthesis in fungi.
• Also inhibits 1st step in cortisol synthesis.
• Inhibits enzymes (side chain cleavage) that inhibit androgen synthesis..
• Side effects include gynecomastia (breast development in males).

Congenital Adrenal Hyperplasia (CAH)

• Enzyme deficiency syndrome causing loss of an enzyme impacting cortisol synthesis.
• This causes a cascade of events with ACTH increasing.
• Various forms exist affecting mineralocorticoids and/or androgens.

CAH Diagnosis

• Screening with newborn blood testing for 17-hydroxyprogesterone.

CAH Treatment

• Treatment replenishes cortisol and stops overproduction of other hormones with glucocorticoids.
• Mineralocorticoids are sometimes used.

Adrenal Disorders

• Excess cortisol, insufficient cortisol, excess mineralocorticoids, and tumors are adrenal disorders.

Cushing's Syndrome

• Syndrome due to high cortisol.
• Most common cause is corticosteroid medication or some inflammatory condition.
• Cushing's disease stems from pituitary ACTH-secreting tumors.

Cushing's Syndrome: Excess Cortisol Effects

• Symptoms include hypertension, hyperglycemia, type 2 diabetes (insulin resistance), immune suppression, high risk for infections, menstrual abnormalities (irregular cycles, oligomenorrhea, amenorrhea), hirsutism in women and/or erectile dysfunction in men, and skin changes (striae, easy bruising.
• Fat redistribution with a "moon face," and/or a "buffalo hump" (fat deposits) can occur.

Cushing's Syndrome: Causes

• ACTH-independent (e.g., adrenal adenoma or glucocorticoid therapy) or-dependent causes (e.g., Cushing's disease from pituitary tumor, or ectopic ACTH from lung cancer).

Cushing's Syndrome: Diagnosis

• Measuring plasma cortisol is difficult due to circadian rhythm (highest in AM).
• Measurement of 24-hour urine free cortisol or salivary cortisol is used; or low-dose dexamethasone suppression tests.
• Differentiating between causes uses high-dose dexamethasone suppression tests.

Cushing's Syndrome: Treatment

• Often includes surgery (removal of adenoma or tumor), and antifungal medications like ketoconazole are sometimes used.

Adrenal Insufficiency

• Insufficient cortisol production, categorized as primary failure of adrenal gland and/or secondary failure of pituitary.

Adrenal Insufficiency: Symptoms

• Cortisol deficiency leads to symptoms like weakness, fatigue, weight loss, postural hypotension, nausea, abdominal pain, diarrhea, and hypoglycemia.
• Aldosterone deficiency leads to hyperkalemia, H+ retention causing acidosis, and sodium loss in urine.

Adrenal Insufficiency: ACTH Effects

• High ACTH levels cause skin hyperpigmentation (common in primary deficiency).
• ACTH stimulates MSH, another hormone.

Addison's Hyperpigmentation

• Generalized darkening of skin in areas exposed to sunlight, elbows, knees, knuckles, areas of pressure.

Adrenal Crisis

• Acute adrenal insufficiency from loss of cortisol and aldosterone causing shock, nausea, vomiting, fatigue, confusion.
• Can be linked to infection.
• Stress dose steroids can help prevent it.

Addison's Disease: Common Causes

• Autoimmune adrenalitis often the cause of antibody and cell-mediated atrophy of the adrenal gland.
• Infections (tuberculosis, fungal like histoplasmosis/cryptococcus, CMV).

Metastasis from Lung Cancer

• Cancer from lungs can spread to the adrenals without symptoms, presenting as a secondary finding from imaging studies..

Waterhouse-Friderichsen Syndrome

• Rare cause of acute adrenal insufficiency.
• Caused by adrenal hemorrhage frequently accompanied by meningococcemia.
• High mortality rate with onset of shock.

Secondary Adrenal Insufficiency

• Most common cause is glucocorticoid therapy causing chronic suppression of ACTH with adrenal atrophy over time.

Secondary Adrenal Insufficiency: Important Points

• Skin findings are absent.
• ACTH is not elevated.
• No hyperkalemia exists.
• Aldosterone is not affected.

Adrenal Insufficiency: Diagnostic Tests

• Measuring serum cortisol at 8 AM is the typical first test.
• A low level suggests adrenal insufficiency.
• Serum ACTH levels measured, with high ACTH suggesting primary disease and low ACTH indicating secondary disease.
• ACTH stimulation test helps further distinguish between primary and secondary.

Primary Aldosteronism

• A mineralocorticoid excess that is often observed at a young age.
• Symptoms include hypertension and hypokalemia (low potassium levels), muscle cramps, and weakness.
• Often, metabolic alkalosis is present

Primary Aldosteronism: Most Common Causes

• Bilateral or idiopathic hyperaldosteronism is most common.
• Aldosterone-producing adenomas are less common, also called Conn's syndrome.

Primary Aldosteronism: Diagnosis

• Measures plasma aldosterone concentration (PAC) and plasma renin activity (PRA).
• Low PRA levels and high PAC indicate primary aldosteronism.
• Distinguishing between bilateral / unilateral disease involves adrenal vein sampling.

Primary Aldosteronism: Treatment

• Surgical adrenalectomy is the definitive treatment for unilateral lesions (adenoma or hyperplasia).
• Spironolactone, a potassium-sparing diuretic, blocks aldosterone effects.

Licorice

• Contains glycyrrhetinic acid (a steroid).
• Weak mineralocorticoid effect, increasing risk of high blood pressure and hypokalemia.
• Lowers 11-beta-hydroxysteroid dehydrogenase activity, lowering the ability of the body to control cortisol levels.

Pheochromocytoma

• A catecholamine-secreting tumor.
• Located in the adrenal medulla.
• Frequently presents with episodic symptoms including hypertension, headaches, palpitations, and sweating. Clinical presentation is episodic in nature.

Pheochromocytoma: Diagnosis

• Serum catecholamine measures are not commonly used.
• Breakdown products are assessed, using 24-hour urine collection or plasma collection.
• Metanephrines (epinephrine/norepinephrine by-products) are measured via metabolism products that accumulate in the urine or blood.
• Vanillylmandelic acid (VMA) is an older but less commonly used method.

Pheochromocytoma: Treatment

• Surgery is the primary treatment for pheochromocytoma.
• Pre-operative management frequently includes alpha-blockers (phenoxybenzamine) to prevent extreme blood pressure fluctuations and beta-blockers (propranolol) during the procedure.

Paraganglioma

• A catecholamine-secreting tumor similar to pheochromocytoma but arises outside of the adrenal medulla.

Neuroblastoma

• Tumor from primitive sympathetic ganglion cells.
• Can arise anywhere in the sympathetic nervous system.
• Frequently adrenal but can be in the abdomen and/or the thorax.

Neuroblastoma: Symptoms

• Often present as abdominal pain.
• Tumor mass effect.

Neuroblastoma: Diagnosis

• Urine catecholamine metabolites (HVA and VMA) are measured via 24-hour urine collection for diagnosis.
• Opsoclonus-myoclonus-ataxia (OMA) can be observed (rapid rhythmic eye movements and ataxia).

Neuroblastoma: Key Risk Factor

• The patient's age at diagnosis frequently influences prognosis and outcome (younger age is better).

MIBG

• Metaiodobenzylguanidine (MIBG) is a chemical analog of norepinephrine.
• Labels sympathetic tissues including tumors for localization via radioactive iodine (I131).

Adrenal Adenomas

• Benign neoplasms that may secrete cortisol or aldosterone.
• May be found incidental on abdominal imaging.
• Non-functional adenomas are often observed over time for growth.
• Functional adenomas are potentially surgical candidates (aldosterone and/or cortisol producing).