PITUITARY FAILURE H Y POPITUITARIS M
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Transcript of PITUITARY FAILURE H Y POPITUITARIS M
PITUITARY FAILURE
HYPOPITUITARISM
DEFINITION
Hipopituitarism is a syndrome produced by complete or partial deficiency of one or more pituitary hormones
The disease develops and insidiously exception be those cases in which hypopituitarism develops during post partum period. The clinical pictures is correlated with etiology of the disease
Hipopituitarism may be primary disease due to disfunction or /and distruction of pituitary gland and secondary, due to the absence of hypothalamic stimulation of the pituitary gland
ETHIOLOGY of HYPOPITUITARISM
The 9 I1. Invasive – is produced by diseases, usually
tumorswhich destroy the pituitary. - Large pituitary tumors destroy the pituitary directly or
by compression of pituitary stalk which produces secondary hypopituitarism
- Chraniophariongiomul produces compressive effects on the hypothalamus and reduces secretion of releasing hormones , it may produces injuries of pituitary stalk or directly destroys the pituitary
- Other CNS tumors may indice hypopituitarism by mass effects over hypothalamic-pituitary system
CHRANIOPHARINGIOMA
ETIOLOGY of HYPOPITUITARISM
The 9 I2. Pituitary infarct – Sheehan syndrome ( first case was published in
1937It results from pituitary infarct of the pituitary due to ischemia during an
important post partum hemorrhage followed by collapse or due to an intravascular coagulation syndrome
Pituitary is more vulnerable to ischemia during post partum period due to its increase in volume due to multiplication of prolactine-secreting cells and and sometimes its vascularity does not increase un the same measure.
32 % of women with severe post partum bleeding develpt a certain degree of post partum hypopituitarism
The pituitary has enough reserves and hypopituitarism develops after 80 % of the gland is destroyed.
Pituitary apoplexy develops during infarct of large tumors with immediately hypopituitarism
ETIOLOGY of HYPOPITUITARISM
The 9 I2. Pituitary infarction – sindromul Sheehan ( first case
published:1937Conditions which lead to pituitary infarction - Large surgery on open hearth, with prolonged hypoxia
urată- Diabetes mellitus associated microangiopathy - During and after radiotherapy for pituitary tumors- Subclinical or silent which determines reduction of
tumroal secretion. (ex. reduction of GH)
Infarct of the pituitary followed by fibrosis
ETIOLOGY of HYPOPITUITARISM
The 9 I3. Pituitary infiltrative diseases- Sarcoidosis infiltrates the hypothalamus and produces secondary
pituitary failure. Sarcoidotic granuloma may destroy the entire hypothalamic-pituitary system with increase in volume of this area and visual field problems similar to those produced by pituitary tumors
- Hemochromatosis: produces hypopituitarism on gonadotropic line and gonadal failure due to gonadal infiltration
- Histiocytosis Langherhans: the infiltration of multiple organs with well differentiated histiocytes may affect the pituitary. This infiltration affects mostly posterior pituitary and the hypothalamus with diabetes insipidus and secondary pituitary failure.
IRM of pituitary infiltrated by histiocytosis
Histicytosis granuloma of the pituitary
Pituitary PET in a patient with histiocytosis and hypopituitarism
ETIOLOGY of HYPOPITUITARISM
The 9 I
4. Injuries – trauma
Cranial trauma during fractures of the base of the skull with section of the pituitary stalk by dura mater and disruption of relatioship between hypothalamus and pituitary;
In childeren with cranial trauma and closed hematoma followed by growth failure.
ETIOLOGY of HYPOPITUITARISM
The 9 I5. ImmunologicalAutoimmune hypophisitis develops during post partum
period and may be diagnosed as post partum pituitary failure
The disease develops slowly and may be associated with other autoimmune diseases such as adrenal failure, premature ovarian failure or autoimmune testicular failure
Pituitary imaging in MRI or CT shows empty sella in post partyum pituitary failure and increased volume of the pituitary in autoimmune hypophisitis due to lymphocytic infiltration of the gland
MRI– autoimmune hypophysitis
MRI – autommune hypophisitis
Lymphocytic infiltration on the pituitary
ETIOLOGY of HYPOPITUITARISM
The 9 I
6. Iatrogenic- The most frequent cause of iatrogenic pituitary failure in surgery
for pituitary or hypothalamic tumors- Pituitary irradiation for CNS tumors in children or for leukemia
may result in hypopituitarism and growth failure- Pituitary irradiation in adult patients with 4500-5000 cGy results in
pituitary failure in 50-60 % of cases- Heavy particles irradiation of the pituitary produces
hypopituitarism in 2-50 % of cases
ETIOLOGY of HYPOPITUITARISM
The 9 I
7. Infectious: tuberculosis , mycosis,
8. Idiopatic1. Isolated of multiple pituitary hormone defficiency
2. Genetic: 1. autosomal recesive or x- linked
2. As part of other genetic syndromes such as Prader Willi syndrome or septo-optic dysplasia
ETIOLOGY of HYPOPITUITARISM
The 9 I9. Isolated
a. Isolated GH deficiency in children may be sporadic or familail and results in growth failure which becomes obvios after 2 years, It may olso appear in emotionally-deprived children, in those with psychological trauma, or physical abused. b. Isolated ACTH may be produce by pituitary failure to synthesize ACTH of due to absence of hypothalamic stimulation. It results in secondary adrenal failure with weakness, hypotension and pale skin
ETIOLOGY of HYPOPITUITARISM
The 9 I9. Isolated
c. Isolated gonadotropin deficiency: most fewquent form is produced by isolated Gn-RH (LH-RH) which may be associated with anosmia (loss of sense of smell) (Kallman’ syndrome) usually in Xp22.3 mutation or isolated. It may be associated with anabillity to recognize colors or deafness.
d. isolated TSH deficiency may be determined by TRH deficiency or chronic kidney failure
e. Isolated prolactine deficiency occurs in autoimmune hypophystis but in most cases prolactine deficiency is a part of multiple pituitary pituitary hormone deficiency
f. Mutiple pituitary hormone deficiency may occur in severe developmental problems of the pituitary due to abnormalities of genes which encodes transcription factors which regulates pituitary development such as PIT-1 and PROP-1
Clinical signs and symptoms of pituitary failure
Clinical signs and symptoms of pituitary hormones:
GH deficiency: growth failure in children and less evident in adult patients:
- Hypoglicaemia, - Decreased lean body mass in increased fat body mass with
increased risk for atherosclerosis- Reduced muscle strength- Weakness- Decreased quality of life
Clinical signs and symptoms of pituitary failure
TSH deficiency- Cold intolerance - Slow thinking and memory troubles- Cold, dry skin- Discrete skin infiltration due to mucopolysacharides accumulation- Bradicardia- Slow muscle reactions
Isolated TSH deficiency
Clinical signs and symptoms of pituitary failure
ACTH deficiency:- Produces adrenal failure with:- Physical, psychological and sexual weakness- Arterial hypotension to shock and colaps- Inability to mobilize cortisole reserves during stress - Pale skin- Loss of sexual hair in axilarry and pubic areas especially
in women whom sexual hair is dependent of adrenal androgens
- Hypoglicaemia aggravated by GH deficiency- In ACTH deficiency there are no signs and symptoms of
aldosteone deficiency and its metabolic consequnces
Clinical signs and symptoms of pituitary failure
Gonadotropin deficiency ( primary or secondary to Gn-RH deficiency
In men:- Decreased sexual desire and sexual function - Testicular atrophy and infertility with azoospermia- Sexual hair loss (beard pubic and axilary hair)
In women: - Secondary (or) primary amenorrhea - Genital atrophy and loss of sexual desire- Sexual hair loss
Severe sexual hair loss and pale skin in a patient with pituitary failure
Panhypopituitarism due to chraniofaringioma
Clinical signs and symptoms of pituitary failure
To the aforementioned signs and symptoms may appear signes depending of the disease which produces the pituitary failure:
- Headache - Narrowing of the visual field in pituitary tumors
Clinical signs and symptoms of pituitary failure
Sheehan’ syndrome:It is a pure form of pituitary failure that occurs in postpartum period
and is recognized in most cases after years of evolution:- Loss of lactation in post partum period- Secondary amenorrhea - Loss of sexual hair in tge following 6 month after pituitary necrosis- Weakness which is physical, psychological and sexual (loss of
sexual desire)- Loss of interest in family and professional life - Anemia- Slow speech, ideas and reactions- Premature ageing
Premature ageing due to Sheehan’s syndrome
MRA in Sheehan’s syndrome
Pituitary coma:It occurs in the following conditions:- Stress exposure- Sedatives - Cold exposure- The occurrence of a disease which needs defending machanisms
dependent of the adrenal function
- Forms:- Hypoglicemic- Hypertermic
Assessment of hypopituitarism
Usual assessment:a. Determination of hormones produced by glands
normally stimulated by pituitary: fT4, cortisole, testosterone, estradiol.
b. Pituitary glands are stimulated with specific tropic hormon and respond confirming that their hypofunction is due to loss of pituitary stimulation :
• ACTH test – if cortisole incrases: pituitary failure• TSH test – if fT4 increases: pituitary failure• LH test: if estradiol or testosterone increase : pituitary
failure
Assessment of hypopituitarism
Ft4 cortisole testosterone estradiolA
TSH ACTH FSH şi LH
Administration in the same injection TRH, CRH şi Gn-RH
TSH, ACTH, FSh şi LH do not increase
TSH, ACTH, FSH şi LH increase
Pituitary failure Hypothalamic failure or interruption of connections between hypothalamus and pituitary
Treatment of hypopituitarismPRINCIPLES
• The usual treatment uses hormones of peripheral glands which are not stimulated by the pituitary
• At the beginning of the treatment the hormones are introduced in the following order: – Cortisole– Thyroxine– Gonadal hormones
Pituitary hormones are used in the following situations: - Induction of fertility in both sexes – Recently GH treatment was introduced in the adult patients, to
improve quality of life, but this is not absolutely needed.
Treatment of hypopituitarism
Dosage– Cortisole: 25 mg/day in 3 devided doses. The morning dose
dose must be the higher. In case of stressful situations cortisole dosage must be increased 4 fold until the stress is terminated.
– Thyroxine – 100 μg/day in one morning dose– Gonadal hormones:
• Men: Testosterone enanthate: 250 mg. monthly or 1000 mg testosterone undecanoate every 3 month, or 25 mg testosterone gel/day (skin application)
• Women: estro-progestitives or Estradiol 1mg /day for 21 days in a month with synthetic progestative in the last 10 days of 21 days of each cycle
Gh DEFICIENCY IN CHILDREN
IT RESULTS IN GROWTH DEFICIENCY. IN CONGENITAL FORMS GROWTH DEFICIENCY APPEARS AS OBVIOUS AFTER THE SECOND YEAR OF LIFE AND IN ACQUIRED FORMS, FROM THE MOMENT IN WHICH GH DEFICIENCY APPEARS.
CAUSES OF GH DEFICIENCY:ENDOCRINE CAUSES
- GH deficiency of different causes- Abnormalities of IGF1 generation in the liver (Laron dwarfs)- Primary IGF1deficiency, pigmeys, IGF1receptor abnormalities- Psychosocial dwarfism- Hypothyroidism- Glucocorticoid excess endogenous or exogenous (iatrogenic)- Type 1 pseudo hypoparathyroidim (Gs alpha protein inactivating
mutation- Diabetes mellitus in children- Adrenal insufficiency
Severe growth failure in a child after long time administration of a potent glucocorticoid -
Dermovate
GH deficiency and hypopituitarism in children
Causes of growth failure:Non-endocrine causes
Constitutional short statureIntrauterine growh retardation IUGRSGA small for gestational
Genetic syndromes associated with growth failure Turner’s syndrome and its variantsNoonan’s syndromePrader Willi syndromeLaurence- Moon Bardet Biedl syndromeChronic diseases during childhood
malabsorbtion CKD
GH deficiency and hypopituitarism in children
Chronic diseases during childhood Hearth diseases Lung diseases Malbsorbtion Afecţiuni hepatice Kidney failure Thalasemia Connective tissue diseases Malnutrition
Genetic syndromes affecting receptivity of cartilages or bones to IGF1
Hypochondrodisplasias Achondroplasia
Turner syndrome and Noonan syndrome
Idiopatic short stature
Silver Russel syndrome
Severe malnutrition
GH deficiency and hypopituitarism in children
Congenital causes• Congenital GH deficiency and its variats• Factors affecting pituitary development: PROP1, PAUF1,
HESX1, LHX1• Median line defects• Pituitary agenesis• Isolated GH deficiency
GH deficiency and hypopituitarism in children
Acquired GH deficiency• Tumors of the hypothalamus or pituitary• Hystiocytosis X• Infections • Cranial trauma• Vascular abnormalities• Cranial iradiations• Hydrocephalus• Empty sella syndrome
GH deficiency and hypopituitarism in children
Abnormalities of IGF1 secretion • Insensivity of GH liver receptors – Laron dwarfs• Primary IGF1 deficiency• Pigmeys• IGF1 receptors deficiency• Psyhosocial dwarfism
GH deficiency and hypopituitarism in children
Evaluation of growth failure in children• Data on birth: length and weight at birth, neonatal
trauma, neonatal hypoxia, micropenis, hypoglicemia, jaudice
• Personal history: cranial trauma, cranial irradiation, CNS infections
• Chronic diseases: anemia, malabsorbtion, severe cardio-vascular diseases, chronic kidney diseases
• Familial history: height of parents and brothers, familial history of short stature, delayed puberty, consaguinity
GH deficiency and hypopituitarism in children
Physical examination. • Growth must be assessed with the same stadiometer
and if possible by the same examinator• Propportion between different segments of the
body,cranial circumference, crown-pubis vs pubic floor distance
• Small penis, undescendent testes
• Growth pattern if such data may be followed
• Screening tests: GH, IGF1, glycaemia, Creatinine and BUN, Bone age
Growth chart
Wrist radiograph for bone age
assessment
GH deficiency and hypopituitarism in children
Classic picture of a child with GHH deficiency
Physical examination. • Heigth at – 2,5 SD raported to normal hegth for age as is
showed in growth charts• Micropenis• History of cranial trauma or hypoxia at birth• Hypogliecaemia at birth or developed after growth
became slowly
GH deficiency and hypopituitarism in children
Classic picture of a child with GH deficiency
Physical examination. • Armonic short stature with normal proportion
between segments of the body• The child has a “doll appearance”• Pale skin with • Abdominal obesity• Small hands and feet • Normal psychological development
Pituitary dwarfism
Pituitary dwarfism
Pituitary dwarfism
Micropenis
GH deficiency and hypopituitarism in children
Laboratory diagnosis in pituitary failure
• Markers of GH function: IGF1, IGFBP3 are less than -2DS
• Other pituitary hormones: TSH, ACTH, LH and FSH are extremely reduced during chidhood
GH deficiency and hypopituitarism in children
Laboratory diagnosis in pituitary failure • If decreased basal Gh, stimulation tests
– Effort stimulation: if Gh increases during a standard effort there is probably not a Gh deficiency (screening non accepted in all clinics
– Hypoglicaemia: insulin stimulation test: 0.05-0.1 IU ordinary insulin is given i.v. and ghicamia and GH are assessed in blood samples every 30 min. At a hypoglicaemia of 0.40 mg./dl or less GH must increased over 10 ng/L
– Arginine stimulation test ).5 mg/kg.bw– Ghrelin stimulation test (ghrelin is a highly potent GH stimulator)– Clonidine stimulation test– At least 2 negative tests are required to prove Gh deficiency
• Test for pituitary of hypothalamic cause –GH-RH test • IGF1generation test: GH is given for 3 days and IGF1 is assessed
before anf after GH
GH deficiency and hypopituitarism in children
Diagnosis of the cause of Gh deficiency
– Sella turcica radiograph– History – MRI of hipothalamo-pituitary and brain: – Abnormalities of medial line– Hypothalamic or pituitary tumors – Empty sella or pituitary hypoplasia
GH deficiency and hypopituitarism in children
GH deficiency treatment:
Recombinant Gh• In small children : 0,016 – 0,035 mg/kg. bw/day• At puberty: 0,035– 0,050 mg/kg. bw/day
• Cortisole and thyroid hormones if multiple pituitary hormone deficiency
• Estradiol and progesterone in girls or testosterone in boys to induce puberty if an appropriate stature was obtained
GH deficiency and hypopituitarism in children
Monitoring Gh treatment
• Bone age – yearly• Thyroid function tests - every 6 month if growth rate
decreases• IGF1, IGFBP3 - very 3 -12 months• GH every 3 month• Hb A1 C every 12 month• Side effects every visit:• Dose modification: based on response: if abnormal
other causes such as malnutrition must be assessed
DEFICITUL DE GH ŞI PANHIPOPITUITARISMUL COPILULUI
Diagnosticul paraclinic nanismului hipofizar - defictului de GH
• Determinarea markerilor acţiunii GH: IGF1, IGFBP3 care sunt mai reduse cu -2DS faţă de normal
• Testul de generare a IGF1 pentru stabilirea diagnosticului diferential intre deficitul de Gh şi cel de lipsa de răspuns la GH se efectuează prin administrare de GH 3 zile şi determinarea IGF1 inainte si dupa test
• Determinarea celorlalti hormoni hipofizari: TSH, ACTH, • Determinarea cauzei hipofizare sau hipotalamice a defictului de
GH – testul la GH-RH sau GH secretagoge
DEFICITUL DE GH ŞI PANHIPOPITUITARISMUL COPILULUI
Tabloul clinc caracteristic al deficitului de GH • Nanism armonic
Depilare si depigmentare severă a unui subiect adult cu insuficienţă hipofizară
IRM in sindromul Sheehan
Fenomeul de imbătrânire prematură în sindromul Sheehan