Endocrinology Flashcards
(8 cards)
Gigantism and Acromegaly
syndromes of excessive secretion of growth hormone (hypersomatotropism) that are nearly always due to a pituitary adenoma. Before closure of the epiphyses, the result is gigantism. Later, the result is acromegaly, which causes distinctive facial and other features. Diagnosis is clinical and by skull and hand x-rays and measurement of growth hormone levels. Treatment involves removal or destruction of the responsible adenoma.
Many growth hormone (GH)–secreting adenomas contain a mutant form of the Gs protein, which is a stimulatory regulator of adenylate cyclase. Cells with the mutant form of Gs protein secrete GH even in the absence of growth hormone–releasing hormone (GHRH). A few cases of ectopic GHRH-producing tumors, especially of the pancreas and lung, also have been described.
Symptoms and Signs
Pituitary gigantism
This rare condition occurs if GH hypersecretion begins in childhood, before closure of the epiphyses. Skeletal growth velocity and ultimate stature are increased, but little bony deformity occurs. However, soft-tissue swelling occurs, and the peripheral nerves are enlarged. Delayed puberty or hypogonadotropic hypogonadism is also frequently present, resulting in a eunuchoid habitus.
Acromegaly
In acromegaly, GH hypersecretion usually starts between the 20s and 40s. When GH hypersecretion begins after epiphyseal closure, the earliest clinical manifestations are coarsening of the facial features and soft-tissue swelling of the hands and feet. Appearance changes, and larger rings, gloves, and shoes are needed. Photographs of the patient are important in delineating the course of the disease.
In adults with acromegaly, coarse body hair increases and the skin thickens and frequently darkens. The size and function of sebaceous and sweat glands increase, such that patients frequently complain of excessive perspiration and offensive body odor. Overgrowth of the mandible leads to protrusion of the jaw (prognathism) and malocclusion of teeth. Cartilaginous proliferation of the larynx leads to a deep, husky voice. The tongue is frequently enlarged and furrowed. In long-standing acromegaly, costal cartilage growth leads to a barrel chest. Articular cartilaginous proliferation occurs early in response to GH excess, with the articular cartilage possibly undergoing necrosis and erosion. Joint symptoms are common, and crippling degenerative arthritis may occur.
Peripheral neuropathies occur commonly because of compression of nerves by adjacent fibrous tissue and endoneural fibrous proliferation. Headaches are common because of the pituitary tumor. Bitemporal hemianopia may develop if suprasellar extension compresses the optic chiasm. The heart, liver, kidneys, spleen, thyroid gland, parathyroid glands, and pancreas are larger than normal. Cardiac disease (eg, coronary artery disease, cardiomegaly, sometimes cardiomyopathy) occurs in perhaps one third of patients, with a doubling in the risk of death from cardiac disease. Hypertension occurs in up to one third of patients. The risk of cancer, particularly of the GI tract, increases 2-fold to 3-fold. GH increases tubular reabsorption of phosphate and leads to mild hyperphosphatemia. Impaired glucose tolerance occurs in nearly half the patients with acromegaly and in gigantism, but clinically significant diabetes mellitus occurs in only about 10% of patients.
Galactorrhea occurs in some women with acromegaly, usually in association with hyperprolactinemia. However, galactorrhea may occur with GH excess alone, because GH itself stimulates lactation. Decreased gonadotropin secretion often occurs with GH-secreting tumors. About one third of men with acromegaly develop erectile dysfunction, and nearly all women develop menstrual irregularities or amenorrhea.
Diagnosis
CT or MRI
Insulin -like growth factor 1 (IGF-1) levels
Usually GH levels
Diagnosis can be made from the characteristic clinical findings. CT, MRI, or skull x-rays disclose cortical thickening, enlargement of the frontal sinuses, and enlargement and erosion of the sella turcica. X-rays of the hands show tufting of the terminal phalanges and soft-tissue thickening.
Treatment
Surgery or radiation therapy
Sometimes pharmacologic suppression of GH secretion or activity
Hypopituitarism
refers to endocrine deficiency syndromes due to partial or complete loss of anterior lobe pituitary function. Various clinical features occur depending on the specific hormones that are deficient. Diagnosis involves imaging tests and measurement of pituitary hormone levels basally and after various provocative stimuli. Treatment depends on cause but generally includes removal of any tumor and administration of replacement hormones.
Hypopituitarism is divided into:
Primary: Caused by disorders that affect the pituitary gland
Secondary: Caused by disorders of the hypothalamus
Symptoms and Signs
Symptoms and signs relate to the underlying disorder and to the specific pituitary hormones that are deficient or absent. Onset is usually insidious and may not be recognized by the patient; occasionally, onset is sudden or dramatic.
Most commonly, growth hormone (GH) is lost first, then gonadotropins, and finally thyroid-stimulating hormone (TSH) and ACTH. Vasopressin deficiency is rare in primary pituitary disorders but is common with lesions of the pituitary stalk and hypothalamus. Function of all target glands decreases when all hormones are deficient (panhypopituitarism).
Lack of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in children leads to delayed puberty. Premenopausal women develop amenorrhea, reduced libido, regression of secondary sexual characteristics, and infertility. Men develop erectile dysfunction, testicular atrophy, reduced libido, regression of secondary sexual characteristics, and decreased spermatogenesis with consequent infertility.
GH deficiency may contribute to decreased energy but is usually asymptomatic and clinically undetectable in adults. Suggestions that GH deficiency accelerates atherosclerosis are unproved. Effects of GH deficiency in children are discussed elsewhere.
TSH deficiency leads to hypothyroidism, with such symptoms as facial puffiness, hoarse voice, bradycardia, and cold intolerance.
ACTH deficiency results in hypoadrenalism with attendant fatigue, hypotension, and intolerance to stress and infection. ACTH deficiency does not result in the hyperpigmentation characteristic of primary adrenal failure.
Hypothalamic lesions, which can result in hypopituitarism, can also disturb the centers that control appetite, causing a syndrome resembling anorexia nervosa, or sometimes hyperphagia with massive obesity.
Sheehan syndrome, which affects postpartum women, is pituitary necrosis due to hypovolemia and shock occurring in the immediate peripartum period. Lactation does not start after childbirth, and the patient may complain of fatigue and loss of pubic and axillary hair.
Pituitary apoplexy is a symptom complex caused by hemorrhagic infarction of either a normal pituitary gland or, more commonly, a pituitary tumor. Acute symptoms include severe headache, stiff neck, fever, visual field defects, and oculomotor palsies. The resulting edema may compress the hypothalamus, resulting in somnolence or coma.
Treatment
Hormone replacement
Treatment of cause (eg, tumor)
Diabetes Insipidus
(DI) results from a deficiency of vasopressin (ADH) due to a hypothalamic-pituitary disorder (central DI [CDI]) or from resistance of the kidneys to vasopressin (nephrogenic DI [NDI]). Polyuria and polydipsia develop.
Diagnosis is by water deprivation test showing failure to maximally concentrate urine; vasopressin levels and response to exogenous vasopressin help distinguish CDI from NDI.
Treatment is with intranasal desmopressin or lypressin. Nonhormonal treatment includes use of diuretics (mainly thiazides) and vasopressin-releasing drugs, such as chlorpropamide.
3 forms:
Neurogenic (hypothalamic)- Occurs when any organic lesion of the hypothalamus, posterior pituitary or pituitary stalk interferes with ADH synthesis, transport or release
Nephrogenic (renal)
Polydipsic (polydipsia-polyuria syndrome)
Pathophysiology
The posterior lobe of the pituitary is the primary site of vasopressin storage and release, but vasopressin is synthesized within the hypothalamus. Newly synthesized hormone can still be released into the circulation as long as the hypothalamic nuclei and part of the neurohypophyseal tract are intact. Only about 10% of neurosecretory neurons must remain intact to avoid CDI. The pathology of CDI thus always involves the supraoptic and paraventricular nuclei of the hypothalamus or a major portion of the pituitary stalk.
CDI may be complete (absence of vasopressin ) or partial (insufficient amounts of vasopressin ). CDI may be primary, in which there is a marked decrease in the hypothalamic nuclei of the neurohypophyseal system
Hyperthyroidism
Hyperthyroidism may result from increased synthesis and secretion of thyroid hormones (thyroxine [T4] and triiodothyronine [T3]) from the thyroid, caused by thyroid stimulators in the blood or by autonomous thyroid hyperfunction. It can also result from excessive release of thyroid hormone from the thyroid without increased synthesis. Such release is commonly caused by the destructive changes of various types of thyroiditis. Various clinical syndromes also cause hyperthyroidism.
The most common causes overall include
Graves disease
Thyroiditis
Multinodular goiter
Single, autonomous, hyperfunctioning “hot” nodule
Graves disease (toxic diffuse goiter), the most common cause of hyperthyroidism, is characterized by hyperthyroidism and one or more of the following:
Goiter
Exophthalmos
Infiltrative dermopathy
Graves disease is caused by an autoantibody against the thyroid receptor for thyroid-stimulating hormone (TSH); unlike most autoantibodies, which are inhibitory, this autoantibody is stimulatory, thus causing continuous synthesis and secretion of excess T4 and T3. Graves disease (like Hashimoto thyroiditis) sometimes occurs with other autoimmune disorders, including type 1 diabetes mellitus, vitiligo, premature graying of hair, pernicious anemia, connective tissue disorders, and polyglandular deficiency syndrome. Heredity increases risk of Graves disease, although the genes involved are still unknow. The pathogenesis of infiltrative ophthalmopathy (responsible for the exophthalmos in Graves disease) is poorly understood but may result from immunoglobulins directed to the TSH receptors in the orbital fibroblasts and fat that result in release of proinflammatory cytokines, inflammation, and accumulation of glycosaminoglycans. Ophthalmopathy may also occur before the onset of hyperthyroidism or as late as 20 yr afterward and frequently worsens or abates independently of the clinical course of hyperthyroidism. Typical ophthalmopathy in the presence of normal thyroid function is called euthyroid Graves disease.
Pathophysiology
In hyperthyroidism, serum T3 usually increases more than does T4, probably because of increased secretion of T3 as well as conversion of T4 to T3 in peripheral tissues. In some patients, only T3 is elevated (T3 toxicosis). T3 toxicosis may occur in any of the usual disorders that cause hyperthyroidism, including Graves disease, multinodular goiter, and the autonomously functioning solitary thyroid nodule. If T3 toxicosis is untreated, the patient usually also develops laboratory abnormalities typical of hyperthyroidism (ie, elevated T4 and 123I uptake). The various forms of thyroiditis commonly have a hyperthyroid phase followed by a hypothyroid phase.
Symptoms and Signs
Most symptoms and signs are the same regardless of the cause. Exceptions include infiltrative ophthalmopathy and dermopathy, which occur only in Graves disease.
The clinical presentation may be dramatic or subtle. A goiter or nodule may be present. Many common symptoms of hyperthyroidism are similar to those of adrenergic excess, such as nervousness, palpitations, hyperactivity, increased sweating, heat hypersensitivity, fatigue, increased appetite, weight loss, insomnia, weakness, and frequent bowel movements (occasionally diarrhea). Hypomenorrhea may be present. Signs may include warm, moist skin; tremor; tachycardia; widened pulse pressure; atrial fibrillation; and palpitations.
Thyroid storm
Thyroid storm is an acute form of hyperthyroidism that results from untreated or inadequately treated severe hyperthyroidism. It is rare, occurring in patients with Graves disease or toxic multinodular goiter (a solitary toxic nodule is a less common cause and generally causes less severe manifestations). It may be precipitated by infection, trauma, surgery, embolism, diabetic ketoacidosis, or preeclampsia. Thyroid storm causes abrupt florid symptoms of hyperthyroidism with one or more of the following: fever, marked weakness and muscle wasting, extreme restlessness with wide emotional swings, confusion, psychosis, coma, nausea, vomiting, diarrhea, and hepatomegaly with mild jaundice.
Treatment Treatment depends on cause but may include Methimazole or propylthiouracil β-Blockers Iodine Radioactive iodine Surgery
Hypothyroidism
thyroid hormone deficiency. It is diagnosed by clinical features such as a typical facial appearance, hoarse slow speech, and dry skin and by low levels of thyroid hormones. Management includes treatment of the cause and administration of thyroxine.
Hypothyroidism occurs at any age but is particularly common among the elderly. It occurs in close to 10% of women and 6% of men > 65. Although typically easy to diagnose in younger adults, it may be subtle and manifest atypically in the elderly. Hypothyroidism may be
Primary: Caused by disease in the thyroid
Secondary: Caused by disease in the hypothalamus or pituitary
Primary hypothyroidism
Primary hypothyroidism is due to disease in the thyroid; thyroid-stimulating hormone (TSH) is increased. The most common cause is autoimmune. It usually results from Hashimoto thyroiditis and is often associated with a firm goiter or, later in the disease process, with a shrunken fibrotic thyroid with little or no function. The 2nd most common cause is post-therapeutic hypothyroidism, especially after radioactive iodine therapy or surgery for hyperthyroidism or goiter. Hypothyroidism during overtreatment with propylthiouracil, methimazole, and iodide abates after therapy is stopped.
Most patients with non-Hashimoto goiters are euthyroid or have hyperthyroidism, but goitrous hypothyroidism may occur in endemic goiter. Iodine deficiency decreases thyroid hormonogenesis. In response, TSH is released, which causes the thyroid to enlarge and trap iodine avidly; thus, goiter results. If iodine deficiency is severe, the patient becomes hypothyroid, a rare occurrence in the US since the advent of iodized salt.
Iodine deficiency can cause congenital hypothyroidism. In severely iodine-deficient regions worldwide, congenital hypothyroidism (previously termed endemic cretinism) is a major cause of intellectual disability.
Rare inherited enzymatic defects can alter the synthesis of thyroid hormone and cause goitrous hypothyroidism (see Congenital Goiter).
Hypothyroidism may occur in patients taking lithium, perhaps because lithium inhibits hormone release by the thyroid. Hypothyroidism may also occur in patients taking amiodarone or other iodine-containing drugs, and in patients taking interferon-alfa. Hypothyroidism can result from radiation therapy for cancer of the larynx or Hodgkin lymphoma (Hodgkin disease). The incidence of permanent hypothyroidism after radiation therapy is high, and thyroid function (through measurement of serum TSH) should be evaluated at 6- to 12-mo intervals.
Secondary hypothyroidism
Secondary hypothyroidism occurs when the hypothalamus produces insufficient thyrotropin -releasing hormone (TRH) or the pituitary produces insufficient TSH. Sometimes, deficient TSH secretion due to deficient TRH secretion is termed tertiary hypothyroidism.
Symptoms and Signs
Symptoms and signs of primary hypothyroidism are often subtle and insidious. Symptoms may include cold intolerance, constipation, forgetfulness, and personality changes. Modest weight gain is largely the result of fluid retention and decreased metabolism. Paresthesias of the hands and feet are common, often due to carpal-tarsal tunnel syndrome caused by deposition of proteinaceous ground substance in the ligaments around the wrist and ankle. Women with hypothyroidism may develop menorrhagia or secondary amenorrhea.
Carotenemia is common, particularly notable on the palms and soles, caused by deposition of carotene in the lipid-rich epidermal layers Deposition of proteinaceous ground substance in the tongue may cause macroglossia. A decrease in both thyroid hormone and adrenergic stimulation causes bradycardia. The heart may appear to be enlarged on examination and imaging, partly because of dilation but chiefly because of pericardial effusion. Pleural or abdominal effusions also may be noted. The pericardial and pleural effusions develop slowly and only rarely cause respiratory or hemodynamic distress.
Elderly patients have significantly fewer symptoms than do younger adults, and complaints are often subtle and vague. Many elderly patients with hypothyroidism present with nonspecific geriatric syndromes—confusion, anorexia, weight loss, falling, incontinence, and decreased mobility. Musculoskeletal symptoms (especially arthralgias) occur often, but arthritis is rare. Muscular aches and weakness, often mimicking polymyalgia rheumatica or polymyositis, and an elevated CK level may occur. In the elderly, hypothyroidism may mimic dementia or parkinsonism.
Although secondary hypothyroidism is uncommon, its causes often affect other endocrine organs controlled by the hypothalamic-pituitary axis. In a woman with hypothyroidism, indications of secondary hypothyroidism are a history of amenorrhea rather than menorrhagia and some suggestive differences on physical examination. Secondary hypothyroidism is characterized by skin and hair that are dry but not very coarse, skin depigmentation, only minimal macroglossia, atrophic breasts, and low BP. Also, the heart is small, and serous pericardial effusions do not occur. Hypoglycemia is common because of concomitant adrenal insufficiency or growth hormone deficiency.
Treatment
l-Thyroxine, adjusted until TSH levels are in midnormal range
Hyperparathyroidism and Hypoparathyroidism
• Hyperparathyroidism is the principle disease of parathyroid glands. Hyperparathyroidism occurs when one (or more) of the parathyroids develops a tumour which makes too much hormone leading to high calcium and other bad symptoms. This tumour must be removed.
• Hypoparathyroidism is the combination of symptoms due to inadequate parathyroid hormone production. This is a very rare condition, and most commonly occurs because of damage to or removal of parathyroid glands at the time of parathyroid or thyroid surgery.
• Hypoparathyroidism is the state of decreased secretion or activity of parathyroid hormone (PTH). This leads to decreased blood levels of calcium (hypocalcaemia) and increased levels of blood phosphorus (hyperphosphatemia).
• Symptoms can range from quite mild (tingling in the hands, fingers, and around the mouth) to more severe forms of muscle cramps. The most severe symptoms are tetany (severe muscle cramping of the entire body) and convulsions (this is very rare).
• Parathyroid gland insufficiency is quite rare, but it can occur in several well-defined ways. The most common cause of hypoparathyroidism is the loss of active parathyroid tissue following thyroid or parathyroid surgery. Rarer is a defect present at birth (congenital), where a person is born without parathyroid glands. Occasionally, the specific cause of hypoparathyroidism cannot be determined.
• 2 types:
o Deficient parathyroid hormone secretion
o Inability of the kidneys and bones to respond to PTH
Cushings
• The term Cushing’s syndrome refers to the manifestations of hypercortisolism from any cause.
• Three important forms of Cushing’ syndrome result from excess glucocorticoid production by the body.
o One is a pituitary form, which results from excessive production of ACTH by a tumour of the pituitary gland; it accounts for about two thirds of the disease cases, and because this form of the disease was the one originally described by Cushing, it is called Cushing’s disease.
o The second form is the adrenal form, caused by a benign or malignant adrenal tumour.
o The third form is ectopic Cushing’s, caused by nonpituitary ACTH-secreting tumour. Cushing’s syndrome can also result from long-term therapy with glucocorticoids; this form is called iatrogenic Cushing’s syndrome.
• The major manifestations of Cushing’s syndrome represent an exaggeration of the many actions of cortisol.
• Altered fat metabolism causes a peculiar deposition of fat characterized by a protruding abdomen; subclavicular fat pads or “buffalo hump” on the back; and round, plethoric “moon face”.
• There is muscle weakness, and the extremities are thin because of protein breakdown and muscle wasting. Osteoporosis may develop because of destruction of bone proteins and alterations in calcium metabolism, resulting in back pain, compression fractures of the vertebrae, and rib fractures.
• Derangements in glucose metabolism are found in about 75% of patients, with clinically overt diabetes mellitus occurring in about 20%.
• The glucocorticoids possess mineralocorticoid properties; this causes hypokalaemia as a result of excessive potassium excretion and hypertension resulting from sodium retention. Inflammatory and immune responses are inhibited, resulting in increased susceptibility to infection.
• Cortisol increases gastric acid secretion, which may provoke gastric ulceration and bleeding. An accompanying increase in androgen levels causes hirsutism, mild acne, and menstrual irregularities in women.
• Excess levels of the glucocorticoids may give rise to extreme emotional lability, ranging from mild euphoria and absence of normal fatigue to grossly psychotic behaviour.
• Untreated, Cushing’s syndrome produces serious morbidity and even death.
Addisons
- Addison’s disease is a chronic metabolic disorder that requires lifetime hormone replacement therapy.
- The adrenal cortex has a large reserve capacity, and the manifestations of adrenal insufficiency do not usually become apparent until about 90% of the gland has been destroyed.
- Mineralocorticoid deficiency causes increased urinary losses of sodium, chloride, and water, along with decreased excretion of potassium. The result is hyponatremia, loss of extracellular fluid, decreased cardiac output, and hyperkalaemia.
- Orthostatic hypotension is common. Dehydration, weakness, and fatigue are common early symptoms. If loss of sodium and water is extreme, cardiovascular collapse and shock ensue. Because of a lack of glucocorticoids, the person with Addison’s disease has poor tolerance to stress.
- This deficiency causes hypoglycaemia, lethargy, weakness, fever, and gastrointestinal symptoms such as anorexia, nausea, vomiting, and weight loss. Hyperpigmentation result from elevated levels of ACTH.
- The skin looks bronzed or suntanned in exposed and unexposed areas. The amino acid sequence of ACTH is strikingly similar to that of melanocyte-stimulating hormone; hyperpigmentation occurs in about 98% of persons with Addison’s disease and is helpful in distinguishing the primary and secondary forms of adrenal insufficiency.
