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Hypothalamic hormones


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GHRH (Growth hormone releasing hormone)

  • Together with somatostatin, it regulates GH secretion
  • It is released in a pulsatile fashion. About 5-9 major pulsues can be detected per day.
  • It's action is enhanced by alpha 2 adrenergic agonists (e.g. clonidine) and opiods.
  • Rigorous exercise enhances the release of GHRH.

USES OF GHRH

  • commercially available form of GHRH is known as sermorellin
  1. To test pituitary function in patients with GH deficiency:
  • GH deficiency could reflect a hypothalamic of pituitary defect.
  • If the primary defect is hypolamic, as is most common, GHRH will elicit an increase in GH release.
  • If the defect is at the level of the pituitary, there will be no increase in GH following GHRH administration.
  1. Therapeutic uses of GHRH to enhance GH secretion:
  • Pulsatile subcutaneous delivery of GHRH, mimicking the normal endogenous patterns (e.g. every 3 hours) has been used to stimulate GH release in patients with GH deficiency that is not of pituitary origin.
  • It can also be administered IV, SC, intranasal.
  • Adverse effects (occasional facial flushing, pallor, headache, etc)

 

SOMATOSTATIN

  • It inhibits the release of growth hormone as well as the release of thyroid stimulatory hormone from the anterior pituitary. It also inhibits the release of most GI hormones (insulin, glucagon and gastrin, etc) thus reducing gastric and pancreatic secretions.

Therapeutic uses

Somatostatin in its naturally occuring form has no clinical value. This is because it has a very short half-life of less than 3 minutes. Also, it has wide spread effects on many secretory systems. 

Octreotide: a synthetic somatostatin analogue with a longer duration of action. 

Lanreotide: is much longer acting, and is administered only twice a month

(subcutaneously or intramuscularly)

  1. It is used in the treatment of hormone secreting tumours: acromegaly, gastrinoma, glucagonoma and carcinoid syndrome.
  2. Pancreatitis, control of esophageal varices bleeding.

AVE: GI disturbances, postprandial hypoglycemia, formation of gall stones, pain at injection sites (lanreotide causes more pain than octreotide). 

 

Thyrotropin releasing hormone

  • It stimulates the release of thyrotropin (TSH) from the anterior pituitary.

It is used in diagnostic testing of thyroid dysfunction, immunoassays are used most often. 

  • Used as a thyroid stimulating hormone reserve.
  • Commercial name: protirelin (IV) AVE: flushing, etc.

 

Corticotropin releasing hormone  

  • It stimulates the secretion of ACTH and beta - endorphin (a closely related peptide) from the anterior pituitary.
  • Synthetic preparations used in the diagnosis of abnormalities of ACTH secretion.
  • to assess whether corticotropin deficiency is due to pituitary or hypothalamus.
  • to evaluate hypothalamic pituitary function after therapy for Cushing's syndrome (to differentiate between the syndrome and ectopic ACTH production).
  • Given IV

AVE: facial flushing, etc.

 

Gonadotropin releasing hormones

  • Stimulate the gonadotrophin cells to produce and release LH and FSH.
  • GnRH (Gonadorelin is a natural occuring GnRH) - administered IV, SC.
  • Gonadorelin analogues: buserelin, nafarelin, leuproreline, triptoreline, goserelin. They are also referred to as GnRH agonists given in pulses to mimic physiologic GnRH which stimulates ovulation. GnRH analogues are administered via SC, IM or nasal spray
  • In contrast, steady dosing inhibits gonadotropin release by causing down-regulation (desentisization) of GnRH receptors in pituitary cells that normally release gonadotropins.

Therapeutic uses

  1. Diagnosis and treatment of hypogonadal states in females and males. It is given by pulsatile treatment in males and females.
  2. Continuous GnRH agonists are used in sex hormone dependent conditions: prostate and breast cancers, uterine fibroid and endometriosis or precocious puberty.

AVE: nose bleeding, weight changes, mood changes, osteoporosis and hypersensitivity reactions. 

 

Prolactin inhibiting hormone

  • Dopamine is the physiologic inhibitor of prolactin release.
  • Because of its peripheral effects and the need for parenteral administration, dopamine is not useful in the control of hyperprolactinemia.

Bromocriptine and other orally active ergot-derivatives which are derivatives of ergometrine or ergotamine. They are dopamine agonists (e.g. cabergoline, pergoline). 

  • They are effective in reducing prolactin secretion from the normal glands as well as from prolactinomas.
  • They are also used in the treatment of acromegaly. NB: Read up clinical uses of bromocriptine.

AVE: Orthostatic hypotension, psychiatric manifestations, constipation, headache, nausea, vomiting: high dosing, confusion, Dry mouth, leg cramps. 

 

Growth hormone  

Activity:

  1. Increases plasma free fatty acids (source of energy for muscle tissue).
  2. Increases hepatic glucose output.
  3. Decreases insulin sensitivity in skeletal muscles.
  4. Is a protein anabolic hormone.

Growth hormone deficiency

  • It can have a genetic basis or be acquired as a result of damage to the pituitary or hypothalamus by a tumour infection, surgery or radiation therapy.
  • In childhood: short stature and adiposity, hypoglycemia.
  • In adulthood: generalised obesity and reduced muscle mass.

Clinical uses of growth hormone (somatotropin) • GH deficiency treatment in children and adults.

  • Children with short stature that is due to factors other than GH deficiency: idiopathic short stature, Turner syndrome or chronic renal failure.

AVE: Hypothyroidism, pancreatic, gynaecomastia, glucose intolerance, lipodystrophy, salt and water retention, pain at injection site. 

  • Possibilities of abuse have also risen e.g. creation of super sports people.
  • Somatrem is an analogue of growth hormone and it has an additional methionine residue and it is more immunogenic than somatotropin. 

Growth hormone excess

  • Mainly benign pituitary tumour
  • In adults, it causes acromegaly.
  • If this occurred before the long gone epiphyses close, it leads to the rare condition, gigantism.

Treatment  

  • Synthetic somatostatin (octreotide)
  • DA agonists (bromocriptine)
  • Surgical removal/ radiotherapy of the tumour.
  • GH Antagonists (Pegvisomat).

 

Thyrotropin-stimulating hormone

Also known as thyrotropin

  • Stimulates secretion of thyroid hormone and growth of thyroid gland.
  • Commercially available analogue - thyrotropin alpha (rh TSH),
  • Route of administration: I.M Diagnostic uses
  • In patients who have been treated surgically for thyroid carcinoma, to test for recurrence, i.e to detect metastatic differentiated thyroid carcinoma.
  • Differentiates between myxoedema (a dermatological change that can occur in hypothyroidism and some forms of hyperthyroidism) due to pituitary dysfunction from primary thyroid disease.
  • Other clinical uses: ???

 

Adrenocorticotropin (ACTH)

  • Stimulates cortisol secretion by the adrenal cortex and promotes growth of adrenal cortex.
  • Therapeutic preparations of ACTH are extracts from the anterior pituitary of domestic animals or synthetic ACTH.
  • Widely used synthetic analogue is Tetracosactide which is mainly gven IM

Diagnotic use  

  • For diagnosis of adrenal cortical insufficiency; blood levels of cortisol is measured by radioimmunoassay after I.M administration of ACTH to address adrenal function and responsiveness.

AVE: Adverse effects of corticosteroids and risk of anaphylaxis. 

 

Follicle stimulating hormone  

  • Females: it stimulates the growth and development of ovarian follicles and promotes the secretion of estrogen by the ovaries.
  • Males: required for sperm production. Three preparations are available for clinical usage:
  1. Urofolitropin: purified from the urine of post menopausal women.
  2. 2 recombinant forms: folitropin alpha and folitropin beta.
  3. These products are used in combination with other drugs to treat infertility in women and men.

 

Luteinizing hormone  

  • Females: responsible for ovulation, formation of corpus lutein in the ovary and regulation of ovarian secretion of female sex hormones.
  • Males: stimulates cells in the testes to secrete testosterone.
  • Lutropin alpha, approved for use in combination with folitropin alpha for stimulating follicular development in infertile women with profound LH deficiency.

 

Prolactin  

Secreted by lactotroph cells of the anterior pituitary which increases in number during pregnancy. 

  • It's secretion is stimulated by estrogen
  • Females: stimulates breast development and milk production
  • Males: involved in testicular function
  • No preparation is available for use in prolactin deficient patients
  • For patients with symptomatic hyperprolactinemia, inhibitipn of prolactin secretion with can be achieved with dopamine agonists which act to inhibit prolactin release.

 

Oxytocin  

  • It is synthesized in the hypothalamus and transported to the posterior pituitary
  • It is an effective stimulant of uterine contractions and is used intravenously to induce or reinforce labour.
  • It induces milk release.

Clinic uses (IV, IM)

  • Induction of labour
  • Control of post partum bleeding

AVE: Fetal distress, placental abruption or uterine rupture and excessive fluid retention. 

 

Vasopressin

  • It is synthesized in the hypothalamus and transported to the posterior pituitary.
  • The function of ADH is to increase water conservation by the kidney.
  • If there is a high level of ADH secretion, the kidneys reabsorb water.
  • If there is low level of ADH secretion, kidneys release water in dilute urine. ADH release increases if BP falls.

Clinical uses 

  • Diabetes insipidus
  • Nocturnal enuresis (by decreasing nocturnal urine production)
  • AVE: hyponatremia and seizures.
  • Synthetic ADH drugs
  • Vasopressin: IV, IM
  • Desmopressin: IV, IM, PO, intranasal.