hypogonadotrophic hypogonadism

7/30/2019 Hypogonadotrophic Hypogonadism

1/43


2/43

HypogonadotrophicHypogonadism(HH)


3/43

CNS-Hypothalamus-Pituitary

Ovary-uterus InteractionNeural control Chemical control

Dopamine

(-)

Norepiniphrine

(+)

Endorphines

(-)

Hypothalamus

Gn-RH

Ant. pituitary

FSH, LH

Ovaries

Uterus

ProgesteroneEstrogen

Menses

?


4/43


5/43


6/43

What is hypogonadotrophic hypogonadism?A state of gonadal hypofunction

(hypoestrognemia-anovulation-

amenorrhea) due to anatomic or

functional disorder in

hypothalamic/pituitarycompartments.


7/43

How does HH presents? In childhood pubertal delay or

arrest and primary amenorrhea.

In sexually mature women it

presents with 2ry amenorrhea.


8/43

Endocrine basis of HH


9/43

1 ry amenorrhea evaluation

Four categories of patients are identified

1. Amenorrhea with absent or poorsecondary sex Characters

2. Amenorrhea with normal 2rysex characters

3. Amenorrhea with signs ofandrogen excess

4. Amenorrhea with absent uterusand vagina


10/43

Kallmann syndrome

Kallmann syndrome is a rare inheriteddisorder.

Three forms are known X-linked, autosomaldominant and autosomal recessive.

The major characteristics of Kallmannsyndrome, in both men and women, are thefailure to experience puberty and thecomplete or partial loss of the sense of

smell. Associated findings might include midline

facial defects, neurosensory deafness,cerebellar ataxia, and epilepsy.


11/43

Kallmann syndrome

In Kallmann syndrome, the GnRH

neurons do not migrate properly from

the olfactory placode to the

hypothalamus during development.

GnRH neurons remain in nasal

epithelium but locally produced Gn-RH

fails to reach pituitary and stimulategonadotrophins.


12/43

Olfactory neurons and Gn-RH neurons


13/43

Idiopathic Hypogonadotrophic

Hypogonadism

Hypoplasia in Gn-RH neurons causingisolated gonadotropin deficiency.

Distinguished from Kallmann syndrome

by olfactory testing with strong odors.Interestingly many of these patients areunaware of their defect.

Treatment in both cases is cyclic hormonal

treatment, or ovulation induction bygonadotropin which requires long time butalmost always successful.


14/43

Other hypothalamic syndromes

Adiposogenital Dystrophy( Babinski-

Froelich Syndrome)

Leurence Moon -Biedel syndrome.

Hypothalamic Infantilism-Obesity

Launois-Cleret Syndrome


15/43

What is pituitary adenoma?

Pituitary adenoma is a tumorof the pituitary gland.

The word adenomaspecifically means tumor ofglandular tissue.

Pituitary adenomas are quitecommon in the generalpopulation. It is estimatedthat around 20% of allindividuals will develop apituitary tumor at some point

during their lifetime, thoughmany do not cause anyproblems and are neverdiagnosed.


16/43

What is pituitary adenoma?

Most pituitary tumors arebenign.

Two-thirds of pituitaryadenomas will remaincompletely confined to thepituitary gland.

Approximately one-third willexpand into tissues that arein the immediate vicinity ofthe pituitary gland, such asthe brain.

Less than one percent of all

pituitary adenomas aremalignant.

Pituitary tumors occur inevery age group but arerarely diagnosed before agetwenty.


17/43

Classification of pituitary adenomas:

The most common type ofpituitary tumor is prolactinoma.These account for nearly 30% ofall pituitary tumors.

The second most prevalenttype, comprising approximately25% of pituitary tumors, iscalled a null cell adenoma. Nullcell adenomas do not produceany hormone.

Growth hormone-secretingtumors, seen in about 10-15% ofpatients, are associated withacromegaly.

Another 10-15% of pituitaryadenomas are accounted for byACTH-secreting tumors, whichare often the cause ofCushing's disease.


18/43

Pituitary lactotrophs

Hypothalamus

PIF (Dopamine)TRH

(-)(+)

Prolactin

Prolactin control


19/43

HyperprolactinemiaCauses: Prolactin secreting pituitary adenoma ( prolactinoma) categorized by size

into microadenoma1 cm.

Non-functioning pituitary adenoma or craniopharyngioma compressing

the pituitary stalk preventing PIF from reaching pituitary.

Primary hypothyroidism because TRH acts as prolactin stimulating

factor.

Iatrogenic due to drugs that inhibit dopaminergic activity through direct

effect on secretion or receptor blockade like metoclopramide,

phenothiazines and opioids.

Chronic renal failure.

Ectopic prolactin secretion by extr-pituitary tumor.

Idiopathic.


20/43

HyperprolactinemiaInvestigations:

Serum prolactin levels. Levels >250 ng/mL are

almost always associated with a prolactinoma.

Magnetic resonance imaging (MRI) with gadolinium

enhancement provides the best visualization of the

sellar area, especially if there is a microadenoma,

defined as a lesion


21/43

Hyperprolactinemia

Clinical presentation:High prolactin levels particularly

with prolactin secreting pituitary

adenoma typically present with

non-peurperal amenorrhea-

Galactorrhea (Forbes-Albright

syndrome)-(Ahumada-Del Castillo

syndrome).


22/43


23/43

Axial CoronalSagital

MRI with gadolinium enhancement


24/43

Hyperprolactinemia

Treatment: Medical treatment is the main stay

using dopamine agonists including

lysergic acid derivatives like

Bromocreptine (Parlodel) and ergots

derivatives like Cabergoline (Dostinex).

Thyroid hormone replacement is

indicated for cases of hypothyroidism.


25/43

HyperprolactinemiaTreatment:

Surgical treatment is considered for tumors

compressing the stalk or causing pressure

symptoms like cranio-pharyngeoma.

Trans-sphenoidal resection of pituitary macro-

prolactinoma but experience is mandatory to avoid

the 2 common complications of CSF rhinorrhea, and

subsequent pan-hypo-pituitarism.

Recently Gamma knife surgery has been introduced

for large tumors with good results.


26/43


27/43


28/43

Sheehans syndrome

Hypertrophy and hyperplasia of lactotrophs during

pregnancy results in the enlargement of the anterior

pituitary, without a corresponding increase in blood

supply.

Secondly, the anterior pituitary is supplied by a low

pressure portal venous system.

These vulnerabilities, when affected by major

hemorrhage or hypotension during the peripartum

period, can result in ischemia of the affectedpituitary regions leading to necrosis.

The posterior pituitary is usually not affected due to

its direct arterial supply.


29/43

Sheehans syndrome

Pituitary necrosis following massiveobstetric hemorrhage.

Pan-hypo-pituitarism might occur

although pituitary cells have differentsensitivity to damage.

The most sensitive are lactotrops followedby gonadotrops then somatotrophs,corticotrops and least are thyrotrops

Therefore the first manifestation is usuallyfailure of lactation.


30/43


31/43

Simmonds Disease

(Pituitary cachexia)

Deficiency of all of pituitary hormones (i.e)pan-hypopituitarism.

The first description of the condition

was made in 1914 by the Germanphysician DrMorris Simmonds.
http://en.wikipedia.org/wiki/Morris_Simmondshttp://en.wikipedia.org/wiki/Morris_Simmonds


32/43

Functional HH (Hypothalamic

amenorrhea)

Eating disorders.

Exercise induced amenorrhea.

Stress induced amenorrhea.

Pseudocyesis.


33/43

The neuronal clamp(hypothalamic gonadostat)

The mechanism whereby

reproduction is shut down

when the nutritional status and

energy balance is shifted or

compromised .


34/43

A Little About the Central Players


35/43

Weight-related amenorrhoea

Anorexia Nervosa

1o or 2o Amenorrhea is often first sign

A body mass index (BMI)


36/43

Anorexia Nervosa

Has a low body weight.

Refuses to keep a normal bodyweight.

Extremely afraid of becomingfat.

Believes she is fat even whenshe's very thin.

Misses three (menstrual)periods for girls/women whohave started having theirperiods.


37/43


38/43

Anorexia Nervosa

AA is a life threateningcondition.

Treatment can beextremely difficult withfrequent relapses.

Intense psychiatricadvice and continuoussupport are mandatory.


39/43

Exercise-associated amenorrhoea

Common in competitiveathletes, long distance runnersand ballet dancers.

Might delay puberty in girlsbeginning before menarche orcause 2ry amenorrhea orirregular cycles.

Low body fat and high levels ofendogenous opioids areresponsible for decrease Gn-RHpulsatility.

O i H h l i


40/43

Organic Hypothalamic-

pituitary destruction

Tumours like craniopharyngeoma, glioma,

and metastasis.

Infilteration like sarcoidosis and

hemochromatosis.

Infections like meningitis or encephalitis.

Trauma like fracture base skull.

Irradiation.


41/43


42/43


43/43

hypogonadotrophic hypogonadism

Documents