Term
| Anterior pituitary derived of |
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Definition
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Definition
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Definition
both lobes
Acts as a neuroendocrine transducer by integrating neural signals from the brain and converting those signals into chemical messages (predominantly peptides) that regulate secretion of pituitary hormones
Finally, pituitary hormones regulate activities of peripheral endocrine organs |
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Term
| Somatotropic hormones consist of |
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Definition
| growth hormone (GH) and prolactin |
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Term
| Glycoprotein hormones consist of |
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Definition
luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH).
Heterodimer, All 3 share the same α-subunit ( also shared by human chorionic gonadotropin (hCG) but each has a unique β-subunit which confers its biological activity |
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Term
| Third class is proteolytic consist of |
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Definition
| Adrenocorticotropin (ACTH) is processed by proteolysis from a larger precursor protein |
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Definition
| End-product inhibition tightly regulates hypothalamic and pituitary gland hormone release referred to the endocrine axis |
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Definition
| Hypothalamic-pituitary-growth hormone (GH) axis regulates general processes that promote growth |
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Term
| insulin-like growth factor (IGF-1) |
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Definition
| Most anabolic effects of GH are mediated by insulin-like growth factor (IGF-1), a hormone released into circulation by hepatocytes in response to stimulation by GH. |
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Definition
| (synthetic form of ACTH) can be used to diagnose adrenal insufficiency |
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Term
| 1° Adrenal insufficiency- |
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Definition
| Administration of cosyntropin to patient with primary adrenal insufficiency will fail to increase plasma cortisol levels (dysfunction of adrenal biosynthesis) |
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Term
| 2° adrenal insufficiency- |
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Definition
Administration of cosyntropin to patient with new-onset secondary adrenal insufficiency will produce robust increase in plasma cortisol
However, long standing 2° adrenal insufficiency may be blunted due to progressive adrenal atrophy |
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Term
| Posterior pituitary hormones influence by hypothalamus |
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Definition
| are synthesized in cell bodies of the supraoptic and paraventricular neurons in the hypothalamus, and then transported down axonal pathways to terminals in the posterior pituitary gland. These hormones are stored in the posterior pituitary gland, from which they are released into the systemic circulation. |
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Term
| anterior pituitary gland influence by hypothalamus |
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Definition
| Neurons in the hypothalamus release regulatory factors that are carried by the hypothalamic–pituitary portal system to the anterior pituitary gland, where they control the release of anterior pituitary hormones. |
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Definition
Stimulated by: GHRH, ghrelin
Inhibited by: Somatostatin
Releases: GH
Targets: Liver, cartilage
Final Production: Insulin-like growth factors |
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Term
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Definition
Stimulated by: TRH
Inhibited by: Dopamine, somatostatin
Releases: Prolactin
Targets: Mammary gland
Final Production: None |
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Definition
Stimulated by: TRH
Inhibited by: Somatostatin
Releases: TSH
Targets: Thyroid
Final Production: Thyroxine, triodothyronine |
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Definition
Stimulated by: CRH
Inhibited by: None Known
Releases: ACTH
Targets: Adreanal Cortex
Final Production: Cortisol, Adrenal androgens |
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Definition
Stimulated by: GnRH
Inhibited by: None Known
Releases: LH, FSH
Targets: GOnads
Final Production: Estrogen, progesterone, and testosterone |
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Term
| Primary endocrine disorder- |
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Definition
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Term
| Secondary endocrine disorder |
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Definition
| reflects pituitary disease |
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Term
| Tertiary endocrine disorder |
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Definition
| reflects hypothalamus pathology |
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Definition
| act as a surrogate for GH activity that is stable throughout the day; IGF-1 levels are a more appropriate tool than GH levels for screening acromegaly |
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Term
| Environmental and Biological factors that increase GH Release |
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Definition
Environmental factors that increase GH Release: hypoglycemia, sleep, exercise, and adequate nutritional status can increase GH secretion
Biological factors that increase GH Release: Growth hormone-releasing hormone (GHRH), sex steroids (notably at puberty), dopamine, ghrelin promote GH release
Ghrelin endogenous growth-hormone releasing peptide which acts synergistically with GHRH to promote GH release that act on a receptor that is distinct from the GHRH receptor.
Ghrelin is secreted by gastric fundal cells during fasting status, linking growth with nutritional status and energy balance
Non-peptide orally active ghrelin mimetics are currently in clinical investigation as GH secretagogues and antagonists are being studied for appetite control |
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Term
| Environmental and Biological factors that decrease GH Release |
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Definition
Environmental factors that decrease GH Release: hyperglycemia, sleep deprivation, poor nutritional status
Biological factors that decrease GH Release: somatostatin, IGF-1, and GH |
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Term
| determine disease etiology of Growth Hormone Deficiency |
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Definition
Semorelin (synthetic GHRH)
Alternative exogenous agents used to stimulate GH release:
Glucagon, arginine, clonidine, and insulin-induced hypoglycemia
Somatropin (recombinant human GH) used for GH-dependent growth retardation
Recombinant IFG-1 generic name (mecasermin) is effective for patients with GH insufficiency (Laron dwarfism) and auto-antibodies against GH (side effects: hypoglycemia, rare intracranial hypertension) |
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Term
| Octreotide and lanreotide- |
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Definition
| synthetic peptides of somatostatin |
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Definition
also a hypothalamic factor that acts on lactotrophs to inhibit prolactin release
DA also stimulates somatotrophs to release GH under physiologic conditions but patients with acromegaly can have paradoxical decrease in GH secretion in response to DA
Bromocriptine and cabergoline used as adjunct agents for acromegaly, less effective than SRLs |
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Term
| Treatments for somatotroph |
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Definition
Surgical resection of the adenoma
Somatostatin receptor agonist or Somatostatin receptor ligands (SRLs)- physiologically inhibits GH secretion (ideal for somatotroph adenomas)
Dopamine (DA) analogues- also a hypothalamic factor that acts on lactotrophs to inhibit prolactin rele
GH receptor antagonist |
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Term
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Definition
| is a GH analogue that has been modified in such way that one site binds to the GH receptor with higher affinity than native GH, but the other binding site is inactive |
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Definition
| the anterior pituitary gland secretes GH, but the liver is unresponsive to stimulation by GH. As a result, IGF-1 secretion is reduced (indicated by dashed lines). The decreased feedback inhibition of GH release results in higher plasma levels of GH (thick line). |
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Term
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Definition
| the pathology lies in an unresponsive anterior pituitary gland, which secretes reduced amounts of GH. Because GH levels are low, the liver is not stimulated to produce IGF-1. |
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Definition
| the hypothalamus fails to secrete GHRH appropriately (dashed line); the role of ghrelin in this condition is unknown. Lack of sufficient GHRH results in lack of adequate stimulation of GH secretion by the anterior pituitary gland and, therefore, diminished production of IGF-1. |
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Definition
| GH is most commonly hypersecreted from an anterior pituitary adenoma. Elevated, and unregulated, GH levels result in increased hepatic production of IGF-1, and thus in systemic trophic effects. Because GH secretion occurs via an autonomous adenoma in the pituitary, negative feedback by IGF-1 is usually less effective. |
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Term
| Bromocriptine, cabergoline |
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Definition
| inhibit lactotroph cell growth and used for prolactinomas |
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Definition
| causes Cushing’s syndrome by autonomously producing cortisol (thick line), independent of regulation by ACTH. The excessive cortisol production suppresses ACTH production (dashed line). |
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Term
| ACTH-producing pituitary adenoma |
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Definition
| Cushing’s disease by autonomously secreting excessive levels of ACTH (thick line), which stimulate the adrenal gland to produce increased levels of cortisol (thick line). ACTH secretion by the tumor has a blunted sensitivity to feedback inhibition by cortisol. |
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Term
| ectopic ACTH-secreting tumor |
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Definition
| (such as a small cell carcinoma of the lung) also stimulates the adrenal gland to produce increased levels of cortisol, which suppress pituitary ACTH production. However, circulating ACTH levels remain elevated due to the ectopic-source production of the hormone. |
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Term
| Cushing’s syndrome treatment |
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Definition
Cushing’s syndrome resulting from primary adrenal tumors is treated by surgery or other medical therapies: metyrapone, ketoconazole, mitotane inhibit effects on adrenal steroidgenesis
Mifepristone antagonizes peripheral cortisol receptor binding |
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Term
| Posterior Pituitary Gland (neurohypophysis |
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Definition
Antidiuretic hormone (ADH) produced by magnocellular cells in hypothalamus; these cells in this region possess osmoreceptors that sense change in extracellular osmolality.
Increased osmolality stimulates ADH secretion from nerve terminals in the posterior pituitary gland
ADH binds 2 receptors V1 and V2 receptors
V1 is located in systemic arterioles and mediates vasoconstriction; ADH’s alternative name is vasopressin
V2 is located on nephron, and stimulates cell surface expression of water channels in order to increase water reabsorption in the collecting duct.
These two actions combined regulate vascular tone by:
Increasing blood pressure
Increasing water reabsorption |
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Term
| Disruption of ADH results in two conditions |
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Definition
Excessive ADH secretion: Syndrome of inappropriate ADH (SIADH)
In SIADH, ADH secretion occurs independent of plasma volume status or osmolality
Common cause is ectopic secretion of ADH by small cell carcinoma
Excessive ADH causes hypertension and excessive water retention
Drugs: Conivaptan (mixed V1a and V2 antagonist) and tolvaptan (V2 antagonist) are vasopressin receptor antagonist
Lithium also used to treat SIADH
Deficient ADH secretion: or decreased responsiveness causes diabetes insipidus |
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Term
| Conivaptan (mixed V1a and V2 antagonist) and tolvaptan (V2 antagoni |
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Definition
| vasopressin receptor antagonist |
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Term
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Definition
| used to treat SIADH syndrome of inappropriate antidiuretic hormone hypersecretion |
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Term
| Neurogenic diabetes insipidus- |
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Definition
results from inability of hypothalamic neurons to synthesize or secrete ADH.
Exogenous analogue desmopressin stimulates V2 receptors and robust concentration of urine and decreased thirst |
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Term
| Nephrogenic diabetes insipidus- |
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Definition
results from inability of renal collecting duct cells to respond to ADH (resistance to ADH); may result from mutation in V2 receptor
Desmopressin has no affect on this condition due to insensitivity to ADH
Diuretics (hydrochlorothiazide and amiloride) have a paradoxical affect of preventing excessive loss of free water, by inducing a volume-contracted state, which promotes enhanced absorption of water in proximal tubules and decreases delivery of water to the site of ADH resistance |
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Definition
is a peptide hormone produced by paraventricular cells of hypothalamus
Involved in muscular contraction of milk during lactation and uterine contraction
Used pharmacologically to induce labor |
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Term
| Follicular thyroid cells constitute the majority of thyroid tissue and produce |
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Definition
| thyroxine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) |
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Term
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Definition
by the enzyme thyroid peroxidase; the oxidation reaction creates reactive iodide intermediate that couples specific tyrosine residues on thyroglobulin
Thyroglobulin is a protein synthesized by thyroid follicular cells secreted at apical surface into colloid space
Thyroglobulin iodination is known as organification, which results in thyroglobulin molecules containing monoiodotyrosine (MIT) and diiodotyrosine (DIT) residues which have one or two covalently attached iodines respectively. |
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Definition
generates T3, whereas two DITs creates T4
Majority of plasma T3 is produced by metabolism of T4 |
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Term
| Metabolism of Thyroid Hormones |
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Definition
Thyroid hormone circulates bound to plasma and mostly thyroid binding globulin (TBG) and transthyretin.
T4 predominant; yet T3 has four times the physiological activity of T4 on target tissue.
T4 has half-life in plasma approximately 6days, whereas T3 is only 1 day. |
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Term
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Definition
autoimmune origin) causes hyperthyroidism; IgG autoantibody specific for the TSH receptor AKA thyroid-stimulating immunoglobulin (TsIg) is produced and acts as an agonist
Activates the TSH receptor stimulating release of thyroid hormone; however TsIg is not subject to negative feedback control and continues to stimulate thyroid function even when plasma levels rise toward pathological levels
Autoantibodies act independent of the hypothalamic-pituitary- thyroid axis
Clinical labs show high plasma thyroid hormone levels and low (undetectable) TSH levels and high TsIg levels. |
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Term
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Definition
results in hypothyroidism due to selective destruction of thyroid gland. Gradual inflammatory destruction
Antibodies specific for thyroid proteins (thyroid peroxidase, thyroglobulin) found in the disease
Early during the disease destruction of thyroid follicular cells results in release of store colloid and transient elevated thyroid hormone
Gland is eventually destroyed
Therapy involves pharmacological replacement |
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Term
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Definition
| Excess TSH or TSH mimetics can cause enlargement of the thyroid (hypertrophied) known as goiter |
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Term
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Definition
| , a stimulatory autoantibody autonomously activates the TSH receptor in the thyroid gland, resulting in sustained stimulation of the thyroid gland, increased plasma thyroid hormone (thick lines), and suppression of TRH and TSH release (dashed lines). |
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Term
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Definition
| a destructive autoantibody attacks the thyroid gland, causing thyroid insufficiency and decreased synthesis and secretion of thyroid hormone (dashed lines). Consequently, feedback inhibition on the hypothalamus and anterior pituitary gland does not occur, and plasma TSH levels rise (thick lines). |
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Definition
the L-isomer of T4 is treatment of choice for hypothyroidism
Exception is for myxedema coma, where the faster onset of T3 may provide enhanced recovery from life-threatening hypothyroidism
Monitored by assay of plasma TSH |
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Term
| Treatment of Hyperthyroidism |
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Definition
Inhibitors of Iodide Uptake
Iodide is uptaken by Na+/ I- symporter. Certain anions with approximate atomic radius of iodide such as perchlorate, thiocyanate, and pertechnetate compete with iodide for uptake into the thyroid gland
This results in a decreased amount of iodide available for thyroid hormone synthesis
Effects are not usually immediate due to the large stores of preformed thyroid hormone in colloid
131I- is radioactive iodide isotope that strongly emits β-particles toxic to cells which selectively destroys the thyroid gland
Used to treat thyrotoxicosis, an alternative to surgery; however patients may eventually develop hypothyroidism after 131I-
The goal is to obtain a euthyroid state without precipitating hypothyroidism |
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Term
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Definition
A second clinical pharmacological agent in paradoxically stable inorganic iodide
High levels of iodide inhibit thyroid synthesis and release, which is called the Wolff-Chaikoff effect
This mechanism is thought to downregulate the Na+/ I- symporter in the thyroid gland.
Thyroid hormone synthesis and release returns to normal several days after the plasma iodide concentration is increased
Therefore, inorganic iodide is not efficient for long-term therapy for hyperthyroidism
High iodide dosing reduces size and vascularity of the thyroid gland, thus, iodide is sometimes administered before surgery (easier incision of the gland) |
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Term
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Definition
Propylthiouracil and *methimazole- inhibit thyroid hormone production. Thioamines compete with thyroglobulin for oxidized iodide in the process that is catalyzed by the enzyme thyroid peroxidase
Thioamine competes with oxidized iodide, treatment causes selective decrease in the organification and coupling of thyroid hormone precursor, and thereby inhibits thyroid production
Thioamines may also bind to thyroglobulin, further antagonizing any coupling reactions
Effects are not seen for several weeks due to Thioamines affecting synthesis and stored thyroid hormone
Thioamine treatment typically results in goiter formation (drugs referred to as goitrogens)
Inhibiting thyroid hormone production by thioamines results in upregulation of TSH release by anterior pituitary gland in efforts to reestablish homeostasis.
The gland hypertrophies in an attempt to increase hormone synthesis which leads to goiter
Propylthiouracil - inhibits thyroid peroxidase as well as peripheral T4 to T3 conversion
methimazole- only shown to inhibit thyroid peroxidase
Both can interfere with vitamin K-dependent synthesis of prothrombin leading to hypoprothrombinemia and increased bleeding
*Lithium- is actively concentrated in the thyroid gland, high levels of Li have been shown to inhibit thyroid hormone release from thyroid follicular cells |
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Definition
| inhibits thyroid peroxidase as well as peripheral T4 to T3 conversion |
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Definition
| only shown to inhibit thyroid peroxidase |
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Term
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Definition
| is actively concentrated in the thyroid gland, high levels of Li have been shown to inhibit thyroid hormone release from thyroid follicular cells |
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Term
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Definition
Mechanism and Target : stimulate release of or replace growth hormone or insulin-like growth factor
Clinical Applications: Growth failure in children with GH deficiency, Turner’s syndrome, Prader-Willi Syndrome, Chronic kidney disease, idiopathic short stature, replacement of endogenous GH in adults with GH deficiency
Adverse Effects: increased intracranial pressure, pancreatitis, hyperglycemia, rapid growth of nevi (skin growth), peripheral edema, injection site reaction, headache, arthralgia (joint pain)
Contraindications: patients with closed epiphyses, active intracranial lesion, active malignancy, proliferative diabetic retinopathy |
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Term
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Definition
Mechanism and Target : same as above
Clinical Applications: diagnostic evaluation of plasma growth hormone
Adverse Effects: transient flushing, chest tightness, injection site reaction, antibody development
Contraindications: do not use with other drugs that affect pituitary hormones |
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Term
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Definition
Mechanism and Target : Same as above
Clinical Applications: Laron Dwarfism, GH deficiency with neutralizing antibodies
Adverse Effects: hypoglycemia, increased intracranial pressure, seizure, tonsillar hypertrophy, injection site reaction
Contraindications: patients with closed epiphyses, active malignancy, |
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Term
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Definition
Mechanism and Target : inhibit GH release
Clinical Applications: Acromegaly, flushing and diarrhea from carcinoid tumors, carcinoid crisis, diarrhea from vasoactive intestinal peptide secreting tumors, TSH-producing tumors
Adverse Effects: arrhythmias, bradycardia, hypoglycemia, gallstone formation, abdominal pain, constipation, diarrhea, nausea, vomiting
Contraindications: hypersentivity to octreotide |
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Term
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Definition
Mechanism and Target : antagonize GH receptor
Clinical Applications: Acromegaly
Adverse Effects: hypertension, peripheral edema, paresthesias, dizziness
Contraindications: hypersentivity to pegvisomant, known malignacy |
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Term
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Definition
Mechanism and Target : inhibit pituitary prolactin release
Clinical Applications: amenorrhea and galactorrhea from hyperprolactinemia, acromegaly, Parkinson's disease, premenstrual syndrome
Adverse Effects: dizziness, hypotension, abdominal cramps, nausea
Contraindications: hypersensitivity to ergot derivatives, uncontrolled hypertension, toxemia of pregnancy |
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Term
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Definition
Mechanism and Target : mixed V1/ V2 receptor antagonist
Clinical Applications: euvolemic and hypervolemic hyponatremia (low sodium), heart failure
Adverse Effects: hypertension, orthostatic hypotension, injection site reaction, hypokalemia, increased thirst, polyuria
Contraindications: concurrent use of P450 3A4 inhibitors |
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Term
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Definition
Clinical Applications: diagnosis of thyroid function
Adverse Effects: seizure, anxiety, hyper- hypotension
Contraindications: None indicated |
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Term
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Definition
Mechanism and Target :
Clinical Applications: adjunctive treatment of malignant tumor of thyroid gland
Adverse Effects: dizziness, headache, vomiting, nausea
Contraindications: adrenal insufficiency, coronary thrombosis |
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Term
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Definition
Mechanism and Target : stimulates adrenal cortisol and androgen production
Clinical Applications: diagnosis of adrenocortical function
Adverse Effects: increased intracranial hypertension, psuedotumor cerebri, seizures, heart failure, necrotizing vasculitis, shock, pancreatitis, peptic ulcer, hypokalemic alkalosis, induction of latent diabetes mellitus, bronchospasm
Contraindications: peptic ulcers, scleroderma, osteoporosis, systemic fungal infection, ocular herpes simplex, heart failure, hypertension, recent surgery, adrenocortical hyper-function or primary insufficiency, or Cushing’s syndrome |
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Term
| Levothyroxine (T4) and Liothyronine (T3) |
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Definition
Mechanism and Target : replace missing endogenous thyroid hormone with exogenous thyroid hormone
Clinical Applications: hypothyroidism, myxedema coma
Adverse Effects: hyperthyroidism, osteopenia, psuedotumor cerebri (benign intracranial hypertension), seizure, myocardial infarction
Contraindications: acute myocardial infarction, uncorrected adrenocortical insufficiency, untreated thyrotoxicosis |
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Term
| Perchlorate*, Thiocyanate*, Pertechnetate |
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Definition
Mechanism and Target : compete for iodide for uptake into thyroid gland follicular cells via sodium-iodide symporter, thereby decreasing intra-thyroid supply of iodide available for thyroid hormone synthesis
Clinical Applications: hyperthyroidism, radio-contrast agents
Adverse Effects: aplastic anemia, GI irritation
Contraindications: no major contraindications |
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Term
| 131I- (radioactive Iodide)*, Iodide (High Concentrations)* |
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Definition
Mechanism and Target : radioactive iodide emits β-particles that are toxic to thyroid cells; High Iodide concentrations inhibits iodide uptake and organification via Wolff-Chaikoff effect
Clinical Applications: hyperthyroidism
Adverse Effects: may worsen opthalmyopathy in Graves’ Disease, hypothyroidism
Contraindications: pregnancy |
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Term
| Propylthiouracil (PTU)* and methimazole* (Thioureylenes) |
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Definition
Mechanism and Target : inhibits thyroid peroxidase and conversion of T4 to T3. methimazole inhibits thyroid peroxidase
Clinical Applications: hyperthyroidism
Adverse Effects: agranulocytosis, hepatotoxicity, vasculitis, hypothrombinemia, rash, arthralgias
Contraindications: pregnancy, breast feeding (methimazole) |
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