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    The Hypothalamo-Pituitary-Adrenocortical Axis: Dr. Noelle Orata Mount Kenya University

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    vivian
    The document discusses the hypothalamic-pituitary-adrenal (HPA) axis, including its components and how they interact to regulate stress responses and hormone production. It describes the hormones produced by the hypothalamus and pituitary that control the adrenal glands. It then details hormone production and functions in the adrenal cortex and medulla. The document concludes by summarizing several disorders that can result from dysfunction of the HPA axis, such as Cushing's syndrome, Addison's disease, and Conn syndrome.

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    The Hypothalamo-Pituitary-Adrenocortical Axis: Dr. Noelle Orata Mount Kenya University

    Uploaded by

    vivian
    10 views49 pages
    The document discusses the hypothalamic-pituitary-adrenal (HPA) axis, including its components and how they interact to regulate stress responses and hormone production. It describes the hormones produced by the hypothalamus and pituitary that control the adrenal glands. It then details hormone production and functions in the adrenal cortex and medulla. The document concludes by summarizing several disorders that can result from dysfunction of the HPA axis, such as Cushing's syndrome, Addison's disease, and Conn syndrome.

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    10. H-P-A axis

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    The document discusses the hypothalamic-pituitary-adrenal (HPA) axis, including its components and how they interact to regulate stress responses and hormone production. It describes the hormones produced by the hypothalamus and pituitary that control the adrenal glands. It then details hormone production and functions in the adrenal cortex and medulla. The document concludes by summarizing several disorders that can result from dysfunction of the HPA axis, such as Cushing's syndrome, Addison's disease, and Conn syndrome.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    10 views49 pages

    The Hypothalamo-Pituitary-Adrenocortical Axis: Dr. Noelle Orata Mount Kenya University

    Uploaded by

    vivian
    The document discusses the hypothalamic-pituitary-adrenal (HPA) axis, including its components and how they interact to regulate stress responses and hormone production. It describes the hormones produced by the hypothalamus and pituitary that control the adrenal glands. It then details hormone production and functions in the adrenal cortex and medulla. The document concludes by summarizing several disorders that can result from dysfunction of the HPA axis, such as Cushing's syndrome, Addison's disease, and Conn syndrome.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    of 49

    The Hypothalamo-Pituitary-

    Adrenocortical Axis

    DR. NOELLE ORATA


    MOUNT KENYA UNIVERSITY
    Objectives:
    • Identify the components of the Hypothalamo-
    Pitutary-Adrenal (HPA) Axis
    • Identify the factors involved in its control
    • Describe the biosynthesis, structure and actions of
    ACTH
    • Identify the functional zones of the adrenal gland,
    the hormones secreted and their actions
    • Discuss Cushing’s syndrome( and ectopic ACTH
    secretion), Addison’s disease, Conn syndrome and
    Congenital adrenal Hyperplasia
    A. Hypothalamus
    • Contains neurosecretory neurons which synthesize
    peptides and catecholamines.
    • Hormones are released into the systemic
    circulation (target distant tissues) or released in
    the portal circulation to the anterior pituitary
    where they stimulate or inhibit release of the
    anterior pituitary hormones.
    • All the hypothalamic hormones are peptides
    except dopamine, which is a catecholamine.
    HYPOTHALAMIC HORMONES AND THEIR ACTIONS.
    Hormones acting on the anterior pituitary Action
    GnRH Stimulates release of leutinizing hormone
    (LH) and follicular stimulating hormone
    (FSH)
    GHRH stimulates release of growth hormone (GH)

    Somatostatin inhibits GH release

    TRH stimulates release of thyroid stimulating


    hormone (TSH) and prolactin

    Dopamine inhibits prolactin release

    CRH stimulates ACTH release

    Hormones acting on distant tissues Action


    ADH
    Oxytocin
    Anterior pituitary
    A. Glycoprotein family
    Peptide hormones with α(homologous) and β
    subunits (differ)
    • LH: stimulates ovulation and the gonadal
    production of sex
    hormones.
    • FSH:stimulates development of ovarian
    follicules, sperms and estrogen.
    production .
    • TSH: stimulates production and release of
    thyroid hormones
    B. POMC family
    • ACTH
    • ß-lipotropin,
    • ß-MSH)
    • ß-endorphin.
    C. Growth hormone/prolactin family
    • GH
    • Prolactin
    • Actions of ACTH
    – Steroidogenesis.
    – Adrenal growth and responsiveness.
    • Release of ACTH
    – CRH
    – Negative feedback.
    The Adrenal gland
    Cortex (80% of the adrenal)
    Secretions: steroid hormones
    – mineralocorticoids - glomerulosa
    – glucocorticoids - fasciculata
    – androgens- reticularis
    Medulla
    – Epinephrine
    – norepinephrine
    Steroid hormone production
    • Cortisol Effects: Body Responses to
    Stress
    • Permissive effect on glucagon
    • Memory, learning & mood
    • Gluconeogenesis
    • Skeletal muscle breakdown
    • Lipolysis, calcium balance
    • Immune depression
    • Circadian rhythms
    Circardian Rythm
    • Aldosterone
    – mediates action at the level of the distal
    convoluted tubules and collecting tubules of
    the kidneys.
    – Na+ resorption.
    – Increasing plasma Na+ inhibits o further
    aldosterone secretion.
    – In the absence of aldosterone, the ratio of K+
    to Na+ increases; high K+ is a direct
    stimulus to aldosterone secretion.
    a. Sex steroids (testosterone)

    supplemental to gonadal
    production (not crucial to life)
    • Control of Cortisol Secretion: Feedback
    Loops
    – External stimuli
    – Hypothalamic
    – Anterior Pituitary
    – Adrenal cortex
    – Tissues
    Disorders
    • Diseases of the Anterior Pituitary
    • Hypopituitarism
    – Pituitary infarction
    • Sheehan syndrome
    • Hemorrhage
    • Shock
    – Others: head trauma, infections, and tumors
    • Hyperpituitarism
    – e.g. due to pituitary adenoma
    Alterations of Adrenal Function
    • Hyperaldosteronism
    – Primary hyperaldosteronism (Conn
    disease)
    – Secondary hyperaldosteronism
    • Adrenocortical hypofunction
    – Secondary hypocortisolism
    – Primary adrenal insufficiency
    (Addison disease)
    » Idiopathic Addison disease
    Cushing Syndrome
    Cause:prolonged exposure to elevated levels of either endogenous or
    exogenous glucocorticoids.
    • endogenous
    – hypercortisolism :primary adrenocortical neoplasm (usually an adenoma but
    rarely a carcinoma)
    • Carney complex(autosomal dominant micronodular hyperplasia of the
    adrenal)
    • McCune-Albright syndrome(hyperfunction of the adrenal glands that
    may lead to Cushing syndrome.cause of precociouspuberty)
    – Cushing disease( Corticotropinoma)
    (80%). anterior pituitary tumor
    – Nonpituitary ACTH
    • oat cell ca
    • small-cell lung carcinoma,
    • carcinoid tumor,
    • ectopic CRH (rare)

    •
    • Majority : due to exogenous
    gluccocorticoids
    • Of endogenous :70% due to
    Cushing disease, 15% ectopic
    ACTH, 15% primary adrenal
    tumor( Nelson syndrome is
    caused by a large ACTH
    secreting pituitary tumor)
    • F:M -5:1
    • Peak: 25-40 years.
    Differentials
    - Renal failure
    -Strenuous exercise
    -Phenobarbital, phenytoin,Rifampicin
    -Psychiatric illness
    -Chronic alcoholism
    - Depression
    Lab Studies

    • Biochemical evaluation of Cushing


    syndrome if due to endogenous
    overproduction of cortisol:demonstrate high
    serum or urine cortisol levels
    • Urinary free cortisol
    • Urinary free cortisol (UFC) :over a 24-hour
    period.Urinary creatinine excretion used to
    assess the reliability of the collection.
    • Urine free cortisol values higher than 3-4
    times the upper limit of normal are highly
    suggestive of Cushing syndrome
    Dexamethasone suppression tests
    Mimic the physiology of the pituitary
    • 1 mg of dexamethasone at 11 pm with
    measurement of cortisol level at 8 am.
    The serum cortisol level should be less than 2-3
    mcg/dL.
    • 8-mg overnight dexamethasone suppression test, 8
    mg orally at 11 pm, cortisol level at 8 am
    Suppression to less than 50% is suggestive of
    pituitary ACTH production
    CRH

    • Intravenous administration of CRH causes a


    rise in plasma ACTH and cortisol levels in
    pituitary ACTH secretion,
    • In patients with ectopic secretion of ACTH,
    CRH does not affect ACTH or cortisol
    levels.
    17-ketosteroid or other cortisol
    precursors- DHEAS
    • adrenal carcinoma
    plasma ACTH level

    • undetectable in ACTH-independent
    Cushing syndrome
    Alterations of Adrenal Function
    • Disorders of the adrenal cortex
    – Cushing disease
    • Excessive anterior pituitary secretion of ACTH
    – Cushing syndrome
    • Excessive level of cortisol, regardless of cause
    – Hyperaldosteronism
    • Primary hyperaldosteronism (Conn disease)
    • Secondary hyperaldosteronism
    Ct..
    – Adrenocortical hypofunction
    • Primary adrenal insufficiency (Addison disease)
    – Idiopathic Addison disease
    • Secondary hypocortisolism
    – Hypersecretion of adrenal androgens and
    estrogens
    • Feminization
    • Virilization
    Alterations of Adrenal Function

    Disorders of the adrenal medulla


    – Adrenal medulla hyperfunction
    • Caused by tumors derived from the chromaffin cells
    of the adrenal medulla
    – Pheochromocytomas
    • Secrete catecholamines on a continuous or episodic
    basis
    Primary Hyperaldosteronism
    Aetiology
    • Conn syndrome (50-60% of cases)-
    aldosterone producing adenoma
    • Idiopathic hyperaldosteronism(40-50%)
    • Ectopic aldosterone (cell rests in kidney or
    ovary)
    • Adrenocortical carcinomas (rare)
    • Glucocorticoid-remediable
    aldosteronism (GRA) Autosomal
    dominant- gene on chromosome 8
    Secondary hyperaldosteronism
    • Common
    – Congestive cardiac failure
    – Liver cirrhosis with ascites
    – Nephrotic syndrome
    • Less common
    – Renal artery stenosis
    – Sodium losin nephritis
    – Barter syndrome
    – Renin secreting tunors
    Symptoms
    • Few symptoms are specific, and mostly
    they result from hypokalemia and
    alkalosis.
    • Aldosterone, by inducing renal distal
    tubular reabsorption of sodium,
    enhances secretion of potassium and
    hydrogen ions, causing hypernatremia,
    hypokalemia, and alkalosis.
    Differentials
    C-11 hydroxylase deficiency
    • C-17 hydroxylase deficiency
    • Cushing syndrome
    • Hypertension
    • Renin-secreting tumor
    • Exogenous mineralocorticoid
    Lab Studies
    • Routine laboratory studies
    – hypernatremia,
    – hypokalemia,
    – metabolic alkalosis
    • impaired glucose tolerance (20%)( inhibitory
    effect of hypokalemia on insulin action)
    Ct..
    • suppressed renin levels
    • confirmatory test is a 24-hour urine
    aldosterone level obtained after 3 days
    of salt loading.
    Primary adrenocortical insufficiency
    (Adddison disease)
    • due to the destruction or dysfunction of the entire
    adrenal cortex.
    • Acquired immunodeficiency syndrome
    – Opportunistic infections CMV, Mycobacterium
    avium intracellulare, cryptococci, Kaposi sarcoma.
    – glucocorticoid resistance syndrome.
    – use of megestrol acetate(appetite stimulant)
    suppress pituitary ACTH
    Ct..
    • Idiopathic autoimmune Addison
    disease(80%)
    • Chronic granulomatous diseases
    – TB, sarcoidosis, histoplasmosis,
    blastomycosis, and cryptococcosis
    • Hematologic malignancies
    e.g leukemia,lymphomas
    • Metastatic malignant disease- breast ,lung
    Other causes
    • Infiltrative metabolic disorders
    – Amyloidosis and hemochromatosis
    • Abnormalities of beta-oxidation of very-
    long-chain fatty acids(acc. of FA)
    • Drug related causes e.g
    ketoconazole,methadone
    • Abdominal irradiation
    Causes of acute Addison disease

    • Stress:
    – Acute adrenal crisis precipitated by
    infection, trauma, surgery, emotional
    turmoil
    • Bilateral adrenal artery emboli and
    bilateral vein thrombosis
    • Bilateral adrenal hemorrhage eg. due to
    septicaemia
    • Bilateral adrenalectomy
    Secondary Adrenal insufficiency

    Hypothalamic or pituitary
    disease or exogenous steroid causing
    suppression of the hypothalamic /
    pituitary axis leading to atrophy of the
    adrenal cortex
    Lab Studies
    • ACTH stimulation test (Cortrosyn, cosyntropin, or
    Synacthen).
    – increase in the plasma cortisol and aldosterone
    • Other laboratory tests
    – Urinary and sweat sodium also may be elevated
    – elevated blood urea nitrogen (BUN) and creatinine
    due to the hypovolemia
    – Hypercalcemia,
    – Hypoglycemia-increased glucose sensitivity
    – Low thyroid hormone levels with increased TSH
    levels
    – Hyperprolactinemia
    Congenital Adrenal Hyperplasia
    Defn.
    A group of inherited metabolic disorders of adrenal steroid
    hormone biosynthesis
    Etiology:
    • 21Hydroxylase deficiency (95%)- often incomplete-
    adequate cortisol synthesis maintained by increased ACTH
    leading to adrenal hyperlasia
    • 11β Hydroxylase deficiency(majority of the remaining
    5%)
    Pathogenesis
    Accumulation of 17α hydroxyprogestrone and increased
    formation of adrenal androgens
    Clinical features
    • Female
    – Born with ambiguous genitalia
    – If partial later hirsuitism,ammenrrhoea,
    infertility
    • Male
    – Precocious puberty
    Diagnosis
    – Elevated levels of 17α hydroxyprogestrone at least 2
    days after birth
    Management
    – Replacement of cotisol and mineralcorticoids

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