Hormone Level Alterations and Pituitary Diseases

Hormone Level Alterations

• Hormone levels might be significantly altered due to inappropriate amounts of hormone being delivered to the target cell.
• Disorders of endocrine glands can lead to altered hormone levels.
• Failure of feedback systems impacts hormone levels.
• Dysfunctional hormones can cause altered levels.
• Defects in hormone delivery affect hormone levels.
• Inappropriate responses by the target cell can alter hormone levels.
• Abnormalities in receptors can lead to altered hormone levels.
• Intracellular disorders may alter hormone levels.

Hypothalamic-Pituitary System

• The hypothalamic-pituitary system can be interrupted by pituitary stalk interruption, destructive lesions, rupture after head injury, surgical transection, or tumor.
• Loss of hypothalamic hormones causes the pituitary to release inadequate amounts of hormones.

Posterior Pituitary Diseases

• Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) involves hypersecretion of ADH.
• SIADH results from ectopic production of ADH by tumors, pulmonary or CNS disorders, surgery, or medications.
• Clinical manifestations of SIADH are related to hyponatremia and are determined by the severity of the condition.
• Diabetes Insipidus results from an insufficiency of ADH, causing loss of too much water in urine.
• Neurogenic (central) Diabetes Insipidus involves insufficient secretion of ADH.
• Nephrogenic Diabetes Insipidus involves an inadequate response to ADH.
• Manifestations of diabetes insipidus include polyuria, nocturia, and continuous thirst.
• Diabetes insipidus involves decreased production of ADH (vasopressin).
• In diabetes insipidus, there is a lack of normal kidney response to ADH, which is nephrogenic.

Pituitary Gland Disorders

• Hypopituitarism is the absence or failure of anterior pituitary hormones.
• Panhypopituitarism is the deficiency of all six anterior pituitary hormones' functions.
• Hypopituitarism is caused by pituitary infarction, space-occupying lesions/tumors, traumatic brain injury, removal or destruction of the gland, infections, or autoimmune hypophysitis.
• Hyperpituitarism is the hypersecretion of hormones.
• Hyperpituitarism is caused by a benign, slow-growing pituitary adenoma.
• The anterior pituitary can cause hypersecretion of growth hormone.
• Acromegaly occurs when the anterior pituitary makes too much growth hormone, causing body parts like hands, feet, and the face to grow larger.
• Gigantism is a condition where the anterior pituitary produces too much growth hormone in childhood or adolescence, before the bones stop growing, causing abnormal, excessive growth, especially in height.

Thyroid Function and Disorders

• Primary thyroid disorders include dysfunction or disease of the thyroid, increased or decreased thyroid hormone (TH), are idiopathic, and are caused by autoimmune mechanisms.
• Central (secondary) thyroid disorders include disorders of the pituitary gland thyroid stimulating hormone (TSH) production.
• Thyrotoxicosis is a condition due to any cause of increased TH levels.
• Hyperthyroidism is a condition where the thyroid gland makes too much of the hormone thyroxine.
• Hyperthyroidism is caused by Graves disease, toxic multinodular goiter, and solitary toxic adenoma.
• Hyperthyroidism includes increased metabolic rate, heat intolerance, increased body temperature, and hypertension (epinephrine).
• Graves disease is an autoimmune disease caused by the stimulation of the thyroid by antibodies against TSH receptors.
• In hyperthyroidism, a thyrotoxic crisis (thyroid storm) occurs when TH levels rise dramatically and can be fatal.
• Graves disease is autoimmune with antibodies that mimic TSH' (TSHR-Ab) that activate the TSH-receptor (TSHR), which leads to the production of thyroid hormones: T3 and T4.
• Graves disease affects 80% of women, and hereditary and environmental influences play a role.
• Graves symptoms include nervousness, weight loss, tachycardia, heat intolerance, and exophthalmos.
• A goiter is hyperplasia of the thyroids to compensate for decreased efficiency, causing enlargement of the thyroid gland.
• Goiters are not tumors or cancerous, 90% are caused by iodine deficiency.
• Toxic goiters involve a large thyroid gland that contains small rounded masses or nodules, which produces too much thyroid hormones, and occur in the elderly.
• Hypothyroidism involves the deficient production of TH by the thyroid gland.
• Primary hypothyroidism is caused by the loss of thyroid function due to autoimmune thyroiditis, loss of thyroid tissue, medications, and endemic iodine deficiency.
• Central (secondary) hypothyroidism is caused by the failure of the pituitary to synthesize adequate TSH, caused by pituitary tumors and associated treatments.
• Manifestations of Hypothyroidism are decreased metabolic rate, cold intolerance, and lethargy.
• Hashimoto disease is an autoimmune disease causing gradual destruction of thyroid tissue, leading to a hypothyroid condition.
• Congenital hypothyroidism is when thyroid tissue is absent or hereditary defects are in THE synthesis.
• Myxedema is a severe form of hypothyroidism, where the thyroid gland isn't making enough thyroid hormone.
• Myxedema symptoms include decreased breathing, lower blood sodium levels, hypothermia, confusion, mental slowness, and low blood oxygen levels, and high blood carbon dioxide levels.
• Hashimoto thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed.
• Hashimoto involves the formation of anti-thyroid antibodies that attack the thyroid tissue, causing progressive fibrosis, lymphocyte infiltration, and fibrosis.
• Cretinism is severe thyroid hormone deficiency during a critical early phase of central nervous system development in utero, when too little hormone is secreted.
• Cretinism symptoms in infants or children include a lack of weight gain, stunted growth, fatigue, lethargy, poor feeding, thickened facial features, abnormal bone growth, mental retardation, and very little crying.

Other Endocrine Disorders

• Hyperparathyroidism involves increased secretion of parathyroid hormone (PTH).
• Primary hyperparathyroidism involves excess secretion of PTH from one or more parathyroid glands.
• Secondary hyperparathyroidism involves an increase in PTH secondary to chronic hypocalcemia.
• Tertiary hyperparathyroidism develops after a long period of hypocalcemia.
• Hallmark manifestations of hyperparathyroidism are hypercalcemia and hypophosphatemia, causing bones to soften and fracture easily.
• Paget disease is a genetically-linked disorder.
• The pathophysiology of Paget disease involves increased and disorganized bone remodeling, leading to overactive osteoclasts that are eventually replaced by enlarged and softened bony structures.
• Patients with Paget disease complain of deep bone pain, fragile bones, headaches, and hearing loss.
• Paget disease is treated with bisphosphonates to slow or block bone resorption of calcium.
• Calcitonin inhibits bone resorption of calcium by excreting it into the urine.
• Hypoparathyroidism involves abnormally low parathyroid hormone (PTH) levels.
• Hypoparathyroidism is caused by parathyroid damage or the accidental removal of parathyroid glands during thyroid surgery.
• In hypoparathyroidism, blood calcium goes down, the nervous system doesn't function properly, and muscles over contract.
• Diabetes mellitus comprises metabolic diseases characterized by hyperglycemia.
• Diabetes mellitus results from defects in insulin secretion, insulin action, or both.
• Categories of diabetes mellitus include Type 1 (deficiency of insulin, IDDM), Type 2 (insulin resistance, NIDDM), and Gestational (during pregnancy).
• Type 1 diabetes mellitus is a common pediatric chronic disease, accounting for 5 to 10% of all diagnosed cases of diabetes.
• Diabetes (1) mellitus can be idiopathic type 1 or autoimmune type 1, and can involve 80 to 90% cell loss and insulin synthesis decline, leading to the development of hyperglycemia.
• Type 1 diabetes involves immunologically mediated beta cell destruction and apoptosis, and has genetic and environmental factors involved.
• Results from insulin deficiency in type 1 diabetes include hyperglycemia, polydipsia, polyuria, weight loss, and fatigue, and high blood sugar, which is prone to ketoacidosis.
• Type 2 diabetes mellitus involves insulin resistance and decreased insulin secretion by beta cells, with risk factors including a family history, age, obesity, hypertension, poor diet, and history.
• Type 2 diabetes mellitus is caused by genetic and environmental interaction.
• Diet during pregnancy may increase long-term risk for children developing type 2 diabetes.
• Initial insulin resistance in type 2 diabetes is followed by compensatory hyperinsulinemia, which prevents clinical appearance, and loss of beta cells causes deficiency of insulin activity.
• Type 2 diabetes mellitus management involves losing weight, watching diet, taking oral meds, and considering insulin as the last option.
• Symptoms of type 2 diabetes fatigue, pruritus, recurrent infection, visual changes, or symptoms of neuropathy.
• Gestational diabetes mellitus (GDM) involves any degree of glucose intolerance with onset or first recognition during pregnancy.
• Maturity Onset Diabetes of Youth (MODY) involves a decrease in beta-cell function or insulin action affected by autosomal dominant mutations.
• Latent Autoimmune Diabetes in Adults (LADA) is a slow onset form of autoimmune (type 1 diabetes) that is diagnosed in individuals who are older than the usual age of onset of type 1 diabetes.
• Acute diabetes mellitus can lead to hypoglycemia.
• Diabetic ketoacidosis (DKA) involves the presence of ketone bodies in the blood + acidosis and is a life-threatening problem that affects people with diabetes, especially type I.
• In DKA, the liver processes the fat into a fuel called ketones, which causes the blood to become acidic.
• Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS) involves severe hyperglycemia but no ketoacidosis.
• Chronic diabetes mellitus can lead to microvascular diseases such as diabetic retinopathy, diabetic nephropathy, and diabetic neuropathies.
• Macrovascular disease related to chronic diabetes mellitus includes cardiovascular disease, CVA (stroke), and peripheral vascular disease leading to infection.
• Disorders of the adrenal cortex involve hypercortical function.
• Cushing syndrome involves manifestations resulting from chronic excess cortisol, regardless of cause.
• Cushing disease involves excessive anterior pituitary secretion of ACTH.
• Adrenal cortex manifestations include weight gain in the trunk (“truncal obesity”), a facial appearance (“moon face”), cervical areas (“buffalo hump”), glucose intolerance, and protein wasting.
• Addison disease is an autoimmune disease causing antibodies to attack the cortex of the adrenal glands where cortisol and aldosterone are made.
• Addison disease results in hypoaldosteronism (low Na+, high K+), low cortisol, and increased bronze pigmentation.
• Addison disease lab findings include hyperkalemia, hyponatremia, hypochloremia, and hypoglycemia.
• Diagnosis of Addison's relies on positive response to the ACTH stimulation test.
• Pheochromocytomas cause excessive production of norepinephrine, and symptoms are related to the chronic effects of catecholamine secretion like hypertension, tachycardia, sweating, and severe headache.
• Increased levels of circulating cortisol lead to Cushing disease with symptoms of weight gain, muscle weakness, and hyperpigmentation of the skin.
• An increase in TSIs results in Graves disease.
• Graves disease has two major distinguishing characteristics ophthalmopathy (including bulging eyes) and dermopathy (swelling on the fronts of the legs and red lesions).
• An excessive production of growth hormone results in acromegaly, which is characterized by coarse skin and body hair, increased body odor, and an enlarged tongue.

Summary

• Pituitary gland hyper- and hyposecretion is associated with pituitary gland tumors.
• Growth hormone disorders include acromegaly and giantism.
• ACTH hypersecretion leads to Cushing syndrome.
• Significant topics include Diabetes Insipidus and Diabetes Mellitus.
• Hyperthyroidism includes Graves disease, goiter, and thyroid cancer.
• Hypothyroidism inlcludes Hashimoto disease, myxedema, and cretinism.
• Parathyroid gland disorders include hyperparathyroidism (Paget’s disease) and hyposecretion effects.
• Adrenal gland disorders: Cushing syndrome and Addison's disease.