Thyroid Hormones & Disorders: Key Concepts

Endocrine Glands

• The endocrine system includes: Hypothalamus, Pituitary, Thyroid, Adrenal, Parathyroid, Pancreas, Ovary/Testes, Pineal, and Thymus
• The hypothalamus is the coordinating center.
• The pituitary is the master gland.

Hypothalamus-Pituitary Relationship

• The hypothalamus and pituitary work together to regulate bodily processes.
• Negative feedback loops regulate the release of hormones from the two glands.
• Hypothalamus releases hormones to control the anterior and posterior pituitary.
• The hypothalamus controls the posterior pituitary through neuronal signals.

Pituitary Disorders

• Pituitary disorders can result from hypo or hyper secretion of pituitary hormones.
• Etiologies of pituitary disorders include: pituitary tumors, brain surgery or radiation, CNS infection or inflammation, and trauma or brain injury.

Growth Hormone

• Growth hormone (GH) leads to a decrease in adipose tissue, and an increase in bone growth and muscle mass.
• GH increases blood glucose.

Hyposecretion of Growth Hormone

• Insufficient GH release from the pituitary has different outcomes based on age.
• Hyposecretion of GH can lead to dwarfism, which is defined as being less than 4 ft 10 in.

Somatropin

• Somatropin is a recombinant DNA growth hormone.
• It is used to treat GH deficiency.
• The anterior pituitary GH stimulates overall growth and protein production and reduces glucose use.
• Adverse effects of somatropin include hyperglycemia, hypercalciuria, renal calculi, and inactivation.
• Precautions for somatropin use include: monitoring blood glucose in patients with diabetes, evaluating TSH at baseline for patients with hypothyroidism, and stopping treatment prior to epiphyseal closure.
• Concurrent use of glucocorticoids can counteract growth-promoting effects
• Somatropin can be administered via IM or subcutaneous routes.
• Clinical considerations include: obtaining baseline heigh and weight and monitoring them every 3-6 months, giving the injection 1 hour before bedtime, and monitoring insulin-like growth factor (IGF-1) for efficacy and dose adjustments.

Hypersecretion of Growth Hormone

• Whether hypersecretion of GH leads to gigantism or acromegaly depends on the timing of epiphyseal plate closure. Acromegaly is caused by anterior pituitary hypersecretion of GH in adults after the closure of the growth plate.
• Gigantism is excessive, symmetrical overgrowth of the skeleton and soft tissues observed in children.
• Acromegaly is the overgrowth of soft tissues, cartilage, and connective tissue seen in adults.
• If left untreated, acromegaly has a mortality rate 2-3 times that of the general population, and it may cause cardiovascular disease and hyperglycemia.

Octreotide

• Octreotide is used to treat gigantism or acromegaly.
• It stops GH secretion from the pituitary gland and is 40 times more potent than endogenous somatostatin hormone.
• Adverse effects of octreotide include: cholesterol gallstones, nausea, cramps, diarrhea, and hypo/hyperglycemia Antidysrhythmics can cause conduction delays; monitor cardiac status and monitor blood glucose if the patient is taking insulin concurrently
• Given IM or subcutaneously. Can cause conduction delays; monitor cardiac status and monitor blood glucose if the patient is taking insulin concurrently
• Should be administered with caution is those with diabetes, hypothyroidism, renal disease, gallbladder disease, and in older adults
• Rotate injection sites and allow medication to reach room temperature and administer slowly.

Antidiuretic Hormone (ADH)

• The hypothalamus produces and the posterior pituitary stores ADH.
• ADH controls the water level in the body.
• Promotes reabsorption of water within the kidney.

Syndrome of Inappropriate ADH Secretion (SIADH)

• SIADH is caused by too much ADH.
• Etiologies of SIADH include: critically ill patients, neoplasms, trauma, CNS infections, and DRUGS
• SIADH most commonly occur in Post-op patients (3-5 DAYS)
• SIADH may occur due to the use of Large doses of chemo or radiation.
• Neuro: Brain hemorrhage or surgery is another cause
• SIADH Pathophysiology includes increased water reabsorption by the kidney, higher intravascular volume, and decreased urine output, leading to dilutional hyponatremia.
• The serum Na+ lowers to <134 mEq/L.
• SIADH treatment focuses on addressing volumes overload by restricting the patient's fluid intake to < 800ml/day as the mainstay therapy
• The underlying cause should be addressed, medications may be used like Hypertonic saline, Oral salt tablets, Vasopressin receptor antagonists and Diuretics.

Diabetes Insipidus (DI)

• DI is caused by too little ADH causing dehydration.
• Central DI results from decreased release of ADH, nephrogenic DI results from kidneys not responding to ADH secretion.
• DI presents with large urine outpus (polyuria) of >100 ml/hour, large fluid intake (polydipsia), and dehydration in patients unable to ingest fluids.
• Lab findings include hypernatremia (>145 mEq/L) as well as a water deprivation test, indicating dehydration even when the patient cannot concentrate urine.
• Desmopressin is hormone replacement therapy for DI.
• Electrolytes should be monitored.

Desmopressin

• Desmopressin is chemically similar to ADH.
• It is used to treat diabetes insipidus and nocturnal enuresis.
• It acts similarly to ADH and prevents water loss by reducing urine output and helping kidneys reabsorb water.
• Side effects include water intoxication (sleepiness, pounding headache), hypertension, flushing, and tolerance development.
• Desmopressin can be administered via oral, intranasal, subcutaneous, and IV routes.
• If toxicity is expected, notify provider who may restrict water and hold treatment and monitor I&O as well as weight.

SIADH vs DI

• SIADH is characterized by low urinary output, excess ADH leading to overhydration, hyponatremia, and fluid retention.
• DI is characterized by high urinary output, insufficient ADH leading to dehydration, hypernatremia, and fluid loss.
• Both will present with excessive thirst.

Feedback Mechanisms of the Thyroid Gland

1. Stimulus
2. Release of TSH from the pituitary
3. Release of either T3 or T4 from the thyroid
4. Increased metabolic rate in most body cells that respond to T3/T4
5. Negative Feedback

Thyroid Hormones

• TSH stimulates thyroid peroxidase (TPO) to make the two active hormones: triiodothyronine (T3) and thyroxine (T4).
• Thyroid hormones have profound effect on the body by regulating metabolism, cardiac function, neurologic development and function, and growth by promoting maturation of bone.

Diagnosis of Thyroid Disorders

• Providers usually obtain a TSH level first.
• A full thyroid panel is ordered if that comes back as abnormal.
• A full thyroid panel consists of T3, T4, and free T4.

Common Thyroid Disorders

• In Hyperthyroidism excessive stimulation of body's metabolism - Graves' Disease- autoimmune disorder.
• In Hypothyroidism = slowing of metabolism - Hoshimoto's- autoimmune.

Goiter

• Goiter is the abnormal enlargement of the thyroid gland.
• It can result from a lack of iodine in the diet, hypothyroidism, or hyperthyroidism.

Medical Management

• Medical Management for Hypothyroidism is Hormone replacement: Levothyroxine; Low calorie, high fiber diet and Medications for constipation
• Medical Management for Hyperthyroidism is Antithyroid drugs: Propylthiouracil (PTU, Methimazole; Beta-adrenergic blocker-Propranolol; Radioactive Iodine, Surgery

Levothyroxine (synthetic T4)

• Levothyroxine is used for Hashimoto's, which causes hypothyroidism.
• Synthetic T4 is used for replacement.
• Adverse effects include: Too high dose causes symptoms of hyperthyroidism (anxiety, tachycardia, chest pain, tremors, palpitations, heat intolerance, diaphoresis, etc.
• Increased risk of fractures from accelerated bone loss- TSH levels should be monitored at least once a year and patients should take Calcium and Vitamine D
• Increased of heart defects and bone loss, starting dose is lower in older adults
• Increased risk of bleeding with warfarin- breaks down vitamin K, monitor PT/INR
• Increased risk of dysrhythmias when used with catecholamine medications (epinephrine, dopamine, dobutamine, pseudoephedrine)
• Give first thing in the AM on empty stomach with a full glass of water, 1 hour before meals
• Monitor Thyroid panel-after initiated, it takes 6-8 weeks for full therapeutic effect and monitor Bone and signs of cardiac toxicity.

Propylthiouracil (PTU)

• PTU is used for Graves’ disease.
• It inhibits the syntheses of T3 and T4 by interfering with the enzyme thyroid peroxidase (TPO) and blocks conversion of T4 into T3
• Watch out for early signs of (sore throat, fever), monitor CBC at baseline, and discontinued to treat if Liver is injured/ hepatitis
• Decrease the effectiveness of warfarin- monitor INR
• monitor Thyroid Panel, CBC, LFTs, signs of hypothyroidism.
• Very slow onset in reducing symptoms (weeks- months)

Methimazole

• The mechanism of action is the same as PTU.
• It is longer lasting and has shown greater efficacy, so it's often used instead of PTU.
• PTU is preferred during the first trimester of pregnancy to avoid the teratogenic effects of methimazole.

Thyroid Life Threatening Emergencies

• Hyperthyroidism can lead to a Thyroid storm - 20% mortality. Precipitated by trauma, infection, withdrawal of anti-thyroid medication, severe thyroiditis and patients presentation is fever, tachycardia, dehydration, coma, tachypnea, delirium
• Hypothyroidism = myxedema coma presents a 30-60% mortality and can be precipitated by trauma, infections, heart failure, medications. This presents as Coma (not required), altered mental state, diastolic hypertension, hypothermia, hypoventilation

Adrenal Gland

• The medulla secretes catecholamines.
• The cortex secretes androgens and corticosteroids.
• Each zone synthesizes a different steroid hormones
• The outer zona glomerulosa produces mineralocorticoids.
• The middle zona fasciculata produces glucocorticoids.
• The inner zona reticularis produces adrenal androgens.

Mineralocorticoids

• Mineralocorticoids are secreted by the zona glomerulosa.
• Aldosterone is the principal mineralocorticoid.
• It acts on distal tubules and collecting ducts in kidney.
• This leads to increased reabsorption of sodium, bicarbonate and water, and decreased reabsorption of potassium

Glucocorticoids

• Glucocorticoids are secreted by zona fasciculata.
• Cortisol is the principal human glucocorticoid.
• Normal Effects:
  • Increase blood pressure, blood glucose, memory, and attention
  • Decrease immune system response, inflammation (pain), serotonin release

Addison's Disease Overview

• In Addison's disease the adrenal glands aren't functioning (adrenal insufficiency).
  • Primary cause-Autoimmune destruction (most common)
  • secondary cause -Surgery/injury to glands like Hypothalamus issue (lack of CRH or Pituitary issue (lack of ACTH)
  • First presentation after a stressful event such as an infection, trauma, GI illness or other stress

Addison's disease

Clinical Manifestations (adrenal insufficiency) are caused by hyptotension, hypoglycemia, progressive weakness, fatigue, weightloss, and hyperpigmentation (bronze color); include Hypokalemia ,Na+ < 135 mEq/L and K > 5 mEq/L

Hydrocortisone

• Hydrocortisone treats adrenal insufficiency.
• Action -Give physiologic doses to replace what the the adrenal glands is not making,
• Administer orally IV or IM and Monitor blood pressure and electrolytes,
• Doses should be given 2-3 times a day
• Can only be administered for short term to treat condition
• Patients should keep an emergency supply of steroids and take in during times of stress to increase dosage- DO NOT STOP ABRUPTLY

Prototype: Fludrocortisone (mineralocorticoid)

• Use- Adrenal insufficiency and Orthostatic hypotension.
• Acts to Promote increased reabsorption of sodium and loss of potassium from renal distal tubules.
• S/E = Hypertension, Edema, Hypokalemia
• Monitor weight, blood pressure, electrolytes (K+, NA+), Monitor breath sounds, urine output and educate patients on manifestations of sodium to include water retention (weight gain, peripheral edema) and hypokalemia (muscle weakness, irregular pulse) and notify immediately.

Corticosteroid indications

In addition to treating adrenal insufficiency, steroids can be used to treat Allergies, Asthma ,Cancer, Infection, GI, inflammatory and Joint inflammatory and Skin inflammation.

Prototype: Prednisone

• Action Decrease inflammation by reducing the production of cytokines and inhibit the release of inflammatory cytokines.
• Often dose related s/e is Hypertension, Hyperglycemia, Cushing syndrome diagnosis and s/i are osteoporosis, Obesity

Hormonal Contradictives

• Work well and Prevent ovulation by providing negative feedback to pituitary which suppresses the secretion of
• Can prevent LH and FSH.Without release they may be not mature and Ovulation does not occur.

Prototype: Combination oral contraceptive (estrogen + progestin)

• Ethinyl estradiol + drosperinone
• Can be combined by Oral. Dose should be taken for 21 days then allow for a few days break to cause a menses cycle (withdrawal bleeding)

Progesterone

• Contraindications are if pregnant and can used as emergency birth control

Prototype : Levonorgestrel - IUD

• Can prevent pregnancy for 3-7 years on brand, it has not been associated with risk for thrombosis and can lead to uterus lining changes,
• It is inserted Intrauterine device only.

Emergency contraception

• Prevention via pills following unprotected intercourse or intervention birth failure.
• An example with high protection chances is a hormone
• Levonorgestrel
• Most effective when taken timely after events

Menopause HRT

• Supplies physiologic doses hormones to treat unpleasant manifestations of menopause is use is
  • Usually considered not safe for healthy women with no -contraindications, within 10 years menopause -3-5 years and women with a uterus must have an estrogen-progestin combination

Clinical Pearls

• Anterior pituitary hormones: growth hormone, TSH, ACTH, FSH, LH.
• Hormone contraceptives can be combined (estrogen + progestin) or
• progestin only -are vaginal bleeding and heart or stroke disease

Test your knowledge of thyroid hormone regulation, effects, and associated disorders like hypothyroidism and hyperthyroidism. Questions cover diagnostic tests, treatment options, and understanding of the thyroid feedback mechanism.