Pituitary Adenomas: Functioning & Non-Functioning

Primary Adenoma of the Pituitary Gland

• Benign tumors of the pituitary gland, located at the brain's base, arising from pituitary cells
• Affects hormone secretion
• Pituitary adenomas from the abnormal growth of pituitary cells
• Excessive secretion or hyposecretion of hormones, or tumor mass effects may be seen
• Classified as functioning (hormone-secreting) or non-functioning (non-hormone-secreting)
• Functioning adenomas produce hormones like prolactin, GH, ACTH, or TSH
• Non-functioning adenomas compress structures, such as the optic chiasm

Functioning Adenomas

• Prolactin-secreting adenomas can cause galactorrhea, infertility, amenorrhea, and decreased libido
• Growth hormone-secreting adenomas can cause acromegaly (in adults) and gigantism (in children)
• Acromegaly/Gigantism leads to abnormal growth of bones and soft tissues
• ACTH-secreting adenomas can cause Cushing's disease; a state of hypercortisolism
• Cushing's includes high cortisol levels and central obesity
• TSH-secreting adenomas are rare and cause hyperthyroidism

Non-Functioning Adenomas

• Presents with mass effect symptoms like headaches, visual disturbances, and hypopituitarism
• Visual disturbances include bitemporal hemianopia
• Hypopituitarism occurs by compression of normal pituitary tissue
• Hypopituitarism results in deficiencies of hormones like gonadotropins, TSH, and ACTH

Acromegaly

• Characterized by excessive GH secretion
• Typically caused by a growth hormone-secreting pituitary adenoma
• Pituitary adenoma secretes excess GH = overproduction of insulin-like growth factor 1 (IGF-1) in the liver
• Elevated IGF-1 causes abnormal growth of bones and soft tissues
• Gigantism happens in children before epiphyseal plates close (excessive linear growth)
• Acromegaly occurs in adults after closure of epiphyseal plates
• Acromegaly/Gigantism causes acral enlargement

Acromegaly Clinical Manifestations

• Enlarged hands and feet (spade-like hands, widened shoes and rings)
• Coarsened facial features, including a prominent jaw (prognathism), enlarged nose, and thicker lips
• Soft tissue hypertrophy, leading to thickened skin, tongue enlargement (macroglossia), and sleep apnea
• Joint pain due to enlargement of the joints
• Hyperhidrosis (excessive sweating) and oily skin
• Increased risk of cardiovascular disease, including hypertension and cardiomegaly
• Glucose intolerance or diabetes mellitus occurs from GH's insulin-antagonistic effects

Diabetes Insipidus (DI)

• Characterized by excessive urination (polyuria) and thirst (polydipsia)
• Caused by an inability to concentrate urine

Diabetes Insipidus Pathophysiology

• Central Diabetes Insipidus (CDI) is caused by insufficient secretion of antidiuretic hormone (ADH or vasopressin)
• CDI may be caused by damage to the hypothalamus or pituitary gland
• Without ADH, kidneys cannot reabsorb water
• Nephrogenic Diabetes Insipidus (NDI) = kidneys are resistant to ADH despite normal or high hormone levels
• NDI may be caused by genetic mutations, certain drugs (e.g., lithium), or kidney disease

Diabetes Insipidus Clinical Manifestations

• Polyuria (frequent urination) with large volumes of dilute urine
• Polydipsia (excessive thirst) due to dehydration
• Nocturia (frequent waking up to urinate)
• Hypernatremia and dehydration in severe cases
• Dry skin and fatigue due to loss of fluids

Syndrome of Inappropriate ADH Secretion (SIADH)

• There is excessive ADH release
• Leads to water retention and hyponatremia
• Increased ADH secretion can occur after surgery for 5 to 7 days

SIADH Pathophysiology

• SIADH has excessive ADH secretion from the posterior pituitary or ectopic sources
• Ectopic sources include small cell lung carcinoma, SSRIs, or head injury
• ADH causes kidneys to retain water, leading to water intoxication and dilutional hyponatremia
• Excessive water retention dilutes sodium in the blood = hyponatremia and cerebral edema

SIADH Clinical Manifestations

• Hyponatremia with symptoms ranging from mild to severe
• Mild-Severe symptoms include nausea, vomiting, and anorexia
• Confusion, lethargy, and in severe cases, seizures or coma due to cerebral edema
• Decreased urine output despite normal fluid intake
• Weight gain due to fluid retention
• Absence of edema

Summary of Key Points for Pituitary Gland Disorders

• Pituitary Adenoma is a tumor causing abnormal hormone secretion or mass effects
• Acromegaly is excessive GH; abnormal growth of bones and soft tissues, usually pituitary adenomas
• Diabetes Insipidus is the inability to concentrate urine; either central (insufficient ADH) or nephrogenic (kidney resistance)
• SIADH is excessive ADH secretion leading to water retention, hyponatremia, and dilutional effects on blood sodium levels

Hyperthyroidism Overview

• Overproduction of thyroid hormones (T3 and T4) by the thyroid gland
• Leads to an accelerated metabolism
• Thyroid gland in the neck plays a crucial role in regulating metabolism, growth, and development through the production of thyroid hormones

Graves' Disease

• Autoimmune disorder-is the most common cause of hyperthyroidism
• More frequently occurs in women, associated with other autoimmune conditions

Graves’ Disease Pathophysiology

• Autoantibodies (thyroid-stimulating immunoglobulins or TSI) are produced and mimic TSH
• TSI antibodies bind to the TSH receptor on thyroid follicular cells
• Excessive stimulation of thyroid hormone gland results (T3 and T4)
• TSI are not regulated by negative feedback = persistent overproduction of thyroid hormones
• Thyroid becomes enlarged (goiter) due to overstimulation and growth of thyroid cells
• Graves' disease can also cause ophthalmopathy (eyes) and dermopathy (legs)

Graves’ Disease Clinical Manifestations

• Increased metabolic rate due to excessive thyroid hormones
• Symptoms of hypermetabolism include weight loss despite increased appetite
• Tachycardia, heat intolerance, tremors and fatigue
• Goiter (enlarged thyroid gland)
• Exophthalmos (bulging eyes) and periorbital edema
• Skin changes such as pretibial myxedema
• Nervousness, irritability, & insomnia are all due to central nervous system impact
• Diarrhea/Increased bowel movements
• Menstrual irregularities, particularly oligomenorrhea or amenorrhea

Thyrotoxic Crisis (Thyroid Storm)

• Life-threatening complication of severe hyperthyroidism
• Can be precipitated by infection, surgery, trauma, or discontinuation of antithyroid medications
• Is considered a medical emergency

Thyrotoxic Crisis Pathophysiology

• Rapid and extreme elevation in thyroid hormone levels
• Causes a hypermetabolic state that affects all organs
• Sudden surge in T3 and T4 levels, usually due to acute exacerbation of underlying hyperthyroidism
• Increased thyroid hormones causes severe tachycardia, hyperthermia, cardiac arrhythmias, and multi-organ dysfunction

Thyrotoxic Crisis Clinical Manifestations

• Severe tachycardia (heart rate > 140 beats per minute) and arrhythmias, especially atrial fibrillation
• Hyperpyrexia (fever) with body temperature often exceeding 40°C (104°F).
• Severe agitation, confusion, and delirium, which can progress to coma in severe cases.
• Profuse sweating due to increased metabolic activity.
• Hypertension, with high systolic pressure and low diastolic pressure due to increased cardiac output.
• Nausea, vomiting, and diarrhea.
• Jaundice due to liver dysfunction.
• Dehydration and electrolyte imbalances.
• Respiratory distress or dyspnea due to increased metabolic demands and possible heart failure.
• Severe weakness or muscle wasting from hypercatabolism.
• Exacerbation of underlying Graves' disease symptoms like goiter, exophthalmos, and tremors.

Graves' Disease vs. Thyroid Storm

• Graves' is chronic, presenting gradually and more subtle, versus acute, life-threatening thyroid storm
• Thyroid storm presents with extreme symptoms and requires immediate intervention

Dx of Hyperthyroidism

• The following lab values may be seen: low TSH, elevated T3 and T4
• In Graves, thyroid-stimulating immunoglobulins (TSI) can be elevated and are diagnostic
• In Graves’ disease, the uptake is typically diffusely increased throughout the thyroid gland
• In toxic multinodular goiter or toxic adenoma, the uptake may be localized to specific areas
• Ultrasound or CT/MRI of the thyroid assesses goiter or structural abnormalities, but is not diagnostic of Grave's

Hyperthyroidism Treatment and Management

• Antithyroid drugs, Beta-blockers, Radioactive iodine therapy and surgical thyroidectomy
• Thyroid Storm Treatment is Beta-blockers, Antithyroid drugs, Iodine therapy, Supportive care and Corticosteroids

Conditions where treatment and management are critical

• Graves' disease leads to weight loss, heat intolerance, tachycardia, goiter, exophthalmos, and pretibial myxedema
• Thyroid storm is a medical emergency triggered by infection or trauma, leading to hyperthermia, severe tachycardia, agitation, and potential multi-organ failure

Iodine and Thyroid Function

• The thyroid gland produces thyroxine (T4) and triiodothyronine (T3) for growth and metabolism.
• T4 contains four iodine atoms and T3 contains three iodine atoms.
• Adequate dietary iodine is needed for T3 and T4 production, and is absorbed from iodized salt, seafood, and dairy products.
• Production of thyroid, T3, and T4 hormones start with tyrosine
• Iodine is transported to the thyroid follicular cells, oxidated, and then bound to thyroglobulin protein and then combined to make MIT and DIT

Iodine Deficiency & Hypothyroidism

• Insufficient iodine prevents production of T3 and T4, increasing TSH from anterior pituitary
• TSH overstimulates thyroid gland due to lack of iodine = Goiter is a result
• Low levels of T3 and T4 result in hypothyroidism

Goiter Formation from Iodine Deficiency

• The thyroid follicular cells hypertrophy and hyperplasia
• This is caused by persistent stimulation of thyroid by high TSH levels
• Goiter is often the first sign of iodine deficiency
• Iodine deficiency related hypothyroidism mirrors other forms of primary hypothyroidism

Related Health Factors

• Infants born to mothers with iodine deficiency have development delays and intellectual disability
• Hallmark feature of iodine deficiency is Goiter which can be visible in the neck
• Compensatory mechanism of the pituitary increased TSH with iodine deficiency caused release more TRH from hypothalamus

Iodine Deficiency Treatments and Prevention

• Elevated TSH and low T3 and T4 are hallmark signs of hypothyroidism
• In iodine deficiency, the TSH is typically elevated
• Prevent and treated with iodized salt or an iodine replacement

Hashimoto's Thyroiditis

• Autoimmune thyroiditis aka Hashimoto's thyroiditis is the destruction of thyroid cells by the body's immune system
• Body is mistakenly attacking the thyroid gland, leading to inflammation and damage and ultimately impairing thyroid function.

Hashimoto’s Thyroiditis Pathophysiology

• Multiple immune mechanisms are at work
• Primary genetic predisposition
• Certain HLA (human leukocyte antigen) alleles linked with Hashimoto, HLA-DR3 and HLA-DR5 in particular
• Autoantibodies such as anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies target thyroid peroxidase (TPO) and thyroglobulin Helper T-cells (CD4+ T-cells) are activated and infiltrate the thyroid gland, which leads to cytokine release
• Immune response destructs thyroid follicles & infiltration of lymphocytes = thyroid dysfunction
• Pituitary gland increases the release of TSH in an attempt to stimulate the thyroid gland
• The gland may form goiter in the process of being damaged

Hashimoto's Over Time

• Can lead to hypothyroidism which is characterized by low levels of T3 and T4 as well as elevated TSH
• Goiter may be present and can be cause via overstimulation of the thyroid by high TSH levels

Hashimoto's Clinical Manifestations

• Signs start mild, become prominent and apparent with increased disease and are usually hypothyroidism
• Subclinical hypothyroidism has normal T3 and T4 but elevated TSH
• Early stages are often asymptomatic and detected only through blood work

Hashimoto's Progressions

• Body experiences fatigue, weight gain, cold intolerance, dry skin, hair loss, hoarseness, bradycardia
• Patients may also experience muscle weakness, as well as mental sluggishness/Difficulty concentrating
• In extreme cases cardiovascular issues along with pericardial effusion and Bradycardia
• Infertility also results

Diagnosing and Treating Hashimoto's

• Typically diagnosed/tested using: Blood tests, Ultrasounds and Fine Needle Aspirations

Related Details Regarding Hashimoto's

• Blood will reveal elevated TSH levels and low levels of free T4
• Auto-TPO levels can be used to check for signs of antibody
• Thyroid is tested using imaging to detect inflammation
• Levothyroxine is the primary form of T4 being used to treat Hashimoto's

Hyperparathyroidism vs. Hypoparathyroidism

• Caused by excessive parathyroid hormone (PTH) levels versus a deficiency
• Can caused muscle spasms, memory impairment, bone effects, and changes to cardiovascular
• Tests primarily focus for PTH levels and related minerals

Hyperparathyroidism vs. Hypoparathyroidism Details

• Both disorders affect the parathyroid glands and regulate calcium and phosphate balance
• Hyper results in to much calcium release
• Autoimmune disorder are the primary factor of hypoparathyoidism

Hyperparathyroidism Pathophysiology

• Elevated calcium levels (hypercalcemia), kidney stones, altered mental status, muscle fatigue and cardiac arrhythmias may also be caused
• Surgical removal of affected glands generally used

Diabetes Details

• GDM, T1DM, T2DM
• All three variants can cause blindness overtime if left untreated
• GDM and T2DM are very similar
• T2DM is the most common

Diabetes Origins

• T1DM is caused from autoimmune disorders
• T2DM can be from genetic mutations
• GDM can be caused from hormones and pregnancy

Diabetes Overview

• T1DM is caused by a lack of insulin and frequent urination can be a side effect
• The lack of insulin with some variants can cause loss of energy and DKA/Ketoacidosis
• T2DM causes a lot of issues and can also cause fatigue and blurred vison

Treatment of Diabetes

• Can range from injectable insulin to strict glycemic controlled or lifestyle changes and oral medications
• Insulin is typically used for those suffering from T1DM

Metabolic Syndrome (MS) & T2DM

• MS is the pre-cursor the T2DM due to inflammation, visceral fat and lack of insulin resistance
• MS requires having 3 of 5 risk factors which includes Abdominal obesity, Elevated Blood Pressure, Elevated Fasting Blood Glucose and more
• Lifestyle Management such as "Dietary Modifications" and "Weight Loss" are used to reduce the impact

The Endocrine System

• Hypoglycemia can be caused when glucose levels fall to 70 mg/DL
• DMK can be fatal and is primarily with people whom fail to regularly used insulin due lack of bodily production
• When having DKA there can be excessive thirst/urination
• Hypoglycemia can be managed with fast/quick sugar sources such as glucose tablets

Diabetes Overview

• DKA is a sign of severe diabetes, patients often breathe in quick short breaths to make up for lack of CO2 There are 3 known types; diabetes retinopathy, diabetic nephropathy, and diabetic neuropathy, all characterized by blindness and fatigue
• Macrovasculars impact Stroke-Like symptomes which can cause loss of movement and weakness
• People with Diabetes have an easier time receiving diseases and are more sensitive to sickness

DKA Management

• DKA is commonly treated via insulins to replace and help better the symptoms
• Electrolytes are commonly part of management

Chronic Complications - The Processes

• DM effects with overproduction from free radicals this is a process called Oxidative stress
• Under certain condition's glucose is sorbitol = polyol Pathway
• AGE is formed through proteins becoming harmed
• Advanced glycation end-products (AGEs) are also produced through protein damage

Cuhsing's, Cause, Treatment and Manifestation

• Is typically caused by Pituitary Adenomas
• Has an impact on the body
• Can cause weight gain and more with excessive hair growth
• MRI's/Imaging may be able to diagnose and treat
• Can involve easy bruising/skin issues etc

Cuhsing's and Addison

• Cuhsing's commonly causes the body and hair to grow and is caused from having too much energy
• Addison is the extreme opposite; no energy and always lethargic

Adrenal Function

• Adrenal produces salt, sugar etc
• Cortisol helps suppress and manage ADTH

Hormones

• When there are primary elevations in the TH level, the TSH level will secondarily decrease
• Because thyrotropin-releasing hormone stimulates prolactin secretion, prolactin may be elevated in primary hypothalamus