Hormone Levels and Pituitary System

• Significantly altered hormone levels arise from inappropriate amounts of hormone delivered to the target cell.
• Disorders of endocrine glands, failure of feedback systems, dysfunctional hormones, defects in hormone delivery, inappropriate responses by the target cell can also alter hormone levels.
• Additional causes of altered hormone levels include abnormalities in receptors and intracellular disorders.

Hypothalamic Pituitary Systems

• Interruption of the pituitary stalk can disrupt hypothalamic pituitary systems.
• Destructive lesions, rupture after head injury, surgical transection, and tumors can impact the hypothalamic pituitary systems.
• Loss of hypothalamic hormones results in the pituitary releasing inadequate hormone amounts.

Posterior Pituitary Diseases

• Syndrome of inappropriate antidiuretic hormone secretion (SIADH) involves hypersecretion of ADH.
• SIADH is caused by ectopic production of ADH by tumors, pulmonary or CNS disorders, surgery, or certain medications.
• Clinical manifestations of SIADH relate to hyponatremia and its severity.
• Diabetes insipidus involves insufficient ADH, causing excessive water loss in urine.
• Neurogenic (central) diabetes insipidus results from insufficient ADH secretion.
• Nephrogenic diabetes insipidus involves an inadequate response to ADH.
• Symptoms of diabetes insipidus include polyuria, nocturia, and continuous thirst.
• Diabetes insipidus: decreased production of ADH (vasopressin).
• Nephrogenic diabetes insipidus is characterized by a lack of normal kidney response to ADH.

Hypopituitarism and Hyperpituitarism

• Hypopituitarism involves the absence or failure of anterior pituitary hormones.
• Panhypopituitarism refers to a deficiency in all six anterior pituitary hormones.
• Hypopituitarism is caused by pituitary infarction, space-occupying lesions/tumors, traumatic brain injury, removal or destruction of the gland, infections, and autoimmune hypophysitis.
• Hyperpituitarism involves hypersecretion of hormones.
• Hyperpituitarism is caused by benign, slow-growing pituitary adenomas.
• The anterior pituitary's hypersecretion of growth hormone.
• Acromegaly: Too much of the growth hormone.
• Gigantism: Too much growth hormone in childhood or adolescence, resulting in excessive growth.

Thyroid Function

• Primary thyroid disorders involve dysfunction or disease of the thyroid, resulting in altered thyroid hormone (TH) levels; can be idiopathic or caused by autoimmune mechanisms.
• Central (secondary) thyroid disorders originate in disorders of the pituitary gland affecting thyroid-stimulating hormone (TSH) production.
• Thyrotoxicosis is a condition caused by increased TH levels.
• Hyperthyroidism is a condition in which the thyroid gland produces too much thyroxine.
• Causes include Graves disease, toxic multinodular goiter, and solitary toxic adenoma.
• Manifestations are increased metabolic rate, heat intolerance, increased body temperature, and hypertension.
• Graves disease is an autoimmune condition caused by thyroid stimulation.
• Thyroid storm (thyrotoxic crisis): TH levels rise dramatically leading to hyperthyroidism and can be fatal.
• Graves disease involves antibodies (TSHR-Ab) that mimic TSH and activate the TSH receptor (TSHR), increasing T3 and T4 production; 80% of cases are in women and hereditary and environment influences
• Symptoms: nervousness, weight loss, tachycardia, heat intolerance, and exophthalmos.
• Goiter: thyroid hyperplasia to compensate for decreased efficiency, enlarging the thyroid gland.
• Iodine deficiency is the cause 90% of the time
• Toxic goiter: increased T3 and T4 from a simple goiter, often in the elderly.
• Toxic goiter involves a large thyroid gland with nodules that produce too much thyroid hormones.
• Hypothyroidism is deficient TH production by the thyroid gland.
• The primary cause has been thyroid loss caused by autoimmune thyroiditis, medication, or endemic iodine deficiency.
• The secondary cause has been Failure of pituitary to synthesize adequate TSH
• Central (Secondary) hypothyroidism is caused by the pituitary tumor
• Manifestations consist of decreased metabolic rate, cold intolerance, and lethargy.
• Hashimoto disease is an autoimmune disease, gradually destroying thyroid tissue and leading to hypothyroidism.
• Congenital hypothyroidism: absent thyroid tissue or hereditary defects in TH synthesis.
• Myxedema: thyroid makes insufficient thyroid hormone.
• Symptoms: decreased breathing, low blood sodium, hypothermia, confusion, mental slowness, low blood oxygen levels, and high CO2 levels.
• Hashimoto thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed.
• Hashimoto disease involves anti-thyroid antibodies that attack the thyroid tissue, causing progressive fibrosis.
• Lymphocyte infiltration and fibrosis are present.
• Cretinism is a severe thyroid hormone deficiency during early central nervous system development, resulting from too little hormone secretion in utero.s.
• Cretinism symptoms include lack of weight gain, stunted growth, fatigue, lethargy, poor feeding, thickened facial features, abnormal bone growth, mental retardation, and minimal crying.

Parathyroid and Paget Disease.

• Hyperparathyroidism involves increased secretion of parathyroid hormone (PTH).
• Primary hyperparathyroidism involves excess PTH from one or more parathyroid glands.
• Secondary causes are increased PTH secondary to chronic hypocalcemia
• Tertiary hyperparathyroidism develops after prolonged hypocalcemia.
• Hypercalcemia and hypophosphatemia are hallmark manifestations; bones soften and fracture easily.
• Paget disease is a genetically-linked disorder involving increased and disorganized bone remodeling and softening, leading to overactive osteoclasts.
• Paget disease Symptoms include deep bone pain, fragile bones, headaches, and hearing loss.
• Paget disease treatment: Bisphosphonates to slow or block bone resorption.
• Calcitonin inhibits bone resorption by promoting calcium excretion in the urine.
• Hypoparathyroidism involves abnormally low PTH levels caused by parathyroid damage or removal during thyroid surgery.
• Hypoparathyroidism causes decreased blood calcium and impaired nervous system function, leading to muscle over-contraction.

Diabetes Mellitus

• Metabolic diseases are characterized by hyperglycemia and result from defects in insulin secretion, insulin action, or both.
• Type 1 is characterized by insulin deficiency (IDDM),
• Type 2 is characterized by insulin resistance (NIDDM),
• Gestational occurs during pregnancy.
• Type 1 diabetes mellitus is a common pediatric chronic disease, accounting for 5-10% of diagnosed cases.
• Type 1 diabetes mellitus: idiopathic and autoimmune forms.
• type 1 diabetes mellitus: 80-90%.
• Immunologically mediated beta cell destruction and apoptosis.
• Type 1 diabetes involves genetic and environmental factors and results from insulin deficiency, hyperglycemia, polydipsia, polyuria, weight loss, fatigue, high blood sugar, and a proneness to ketoacidosis.
• Type 2 diabetes mellitus arises from insulin resistance and decreased secretion by beta cells; risk factors include family history, age, obesity, hypertension, poor diet, and history.
• Type 2 diabetes: caused by genetic environmental interaction and a higher risk to children.
• Type 2 diabetes mellitus: initial insulin resistance which prevents appearance, but is a loss of beta cells causing deficiency of insulin activity.
• Type 2 diabetes includes: weight loss, diet control, oral meds, and insulin in that order.
• Type 2 diabetes: Fatigue, pruritus, recurrent infection, visual changes or symptoms of neuropathy.
• Gestational diabetes mellitus (GDM): any degree of glucose intolerance with onset or first recognition during pregnancy.
• Maturity onset diabetes of youth (MODY): beta-cell function or insulin action is affected by autosomal dominant mutations.
• Latent Autoimmune Diabetes in Adults (LADA): a slow-onset autoimmune form of type 1 diabetes diagnosed in older individuals.
• Acute diabetes mellitus: Hypoglycemia
• Diabetic ketoacidosis (DKA): ketones bodies in blood +acidosis
• Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS): severe hyperglycemia but no ketoacidosis
• Chronic complications: microvascular and macrovascular diseases.

Other Disorders

• Chronic Diabetes mellitus leads to Microvascular disease like Diabetic retinopathy and Diabetic nephropathy. It also leads to Diabetic neuropathies

• Chronic Diabetes mellitus leads to macrovascular disease;Cardiovascular disease- CVA: Stroke- Peripheral vascular disease-Infection

• Hyper Cortical function is a disorder of the adrenal cortex function

• Cushing syndrome manifestations are a result during chronic excess cortisol

• Cushing disease manifests as excessive anterior pituitary secretion of ACTH.

• Adrenal cortex Manifestations consists of weight gain, facial and cervical features, glucose intolerance and protein wasting.

• Addison disease: Autoimmune disease causing reaction in the cortex of adrenal glands.

• Addison- Results include Hypoaldosteronism (low Na+, high K+), Low cortisol, increased Bronze pigmentation

• Addison Lab findings: Hyperkalemia, Hyponatremia, Hypochloremia, Hypoglycemia

• Addison disease diagnosis: Positive to ACTH stimulation test

• Pheochromocytomas cause excessive norepinephrine production, leading to hypertension, tachycardia, sweating, and severe headaches.

• Increased circulating cortisol: Cushing disease.

• Symptoms: weight gain, muscle weakness, and hyperpigmentation of the skin.

• Increased TSIs: Graves disease.

• Graves disease major characteristics: ophthalmopathy and dermopathy.

• Excessive growth hormone production: Acromegaly

• Symptoms: coarse skin and body hair, increased body odor, and an enlarged tongue

• Pituitary gland hyper- and hyposecretion: pituitary gland tumors

• Growth hormone disorders: Acromegaly, Gigantism

• ACTH Hypersecretion: Cushing Syndrome

• Diabetes Insipidus and Diabetes Mellitus

• Hyperthyroidism-Graves disease, Goiter, Thyroid cancer

• Hypothyroidism- Hashimoto disease and Myxedema, Cretinism

• Parathyroid gland: Hyper (Paget's disease) and Hyposecretions effects

• Adrenal gland: Cushing syndrome and Addison's disease